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  • 1995-1999  (1,083)
  • 1980-1984
  • 1996  (1,083)
  • Organic Chemistry  (539)
  • Cell & Developmental Biology  (458)
  • Nuclear reactions
  • pharmacokinetics
  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and toxicity of oral and intravenous lonidamine in dogs (1996)
    Springer
    Cancer chemotherapy and pharmacology 38 (1996), S. 129-135 
    Details
    ISSN: 1432-0843
    Keywords: Key words lonidamine ; pharmacokinetics ; dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Plasma lonidamine concentration and toxicity were investigated in dogs receiving 100, 200, 400, 800, 1200 mg/m2 orally twice daily for 30 days and in dogs receiving single intravenous doses of 200, 400, 800, 1200 mg/m2. Physical or laboratory signs of toxicity were not observed in dogs receiving oral lonidamine, but severe vomiting and signs of acute hepatic and pancreatic toxicity were observed in dogs receiving intravenous doses that exceeded 400 mg/m2. The area under the lonidamine concentration versus time curve (AUC) in dogs receiving 200, 400, and 800 mg/m2 of lonidamine intravenously was a 1.8-, 3.3-, and 8.7-fold higher than in dogs receiving oral lonidamine. This suggests that the bioavailability of oral lonidamine may be limited. However, centrilobular hepatocellular swelling and vacuolation were observed in dogs receiving oral lonidamine. Serum alanine aminotransferase (ALT) activity was increased in dogs receiving intra-venous lonidamine. These findings suggest that lonidamine is hepatotoxic in dogs. However, serum ALT was increased in only 1/4 dogs receiving 400 mg/m2 of lonidamine intravenously and plasma concentration were within the range capable of sensitizing hyperthermia and chemotherapy. Therefore, this dose and route appears to be a viable and controllable method for prospective quantification of lonidamine interaction with systemic chemotherapy and/or hyperthermia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050460
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of dexamethasone in premature neonates (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 477-483 
    Details
    ISSN: 1432-1041
    Keywords: Dexamethasone ; Premature neonates ; pharmacokinetics ; bronchopulmonary dysplasia ; infant ; newborn
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Dexamethasone is frequently used in premature neonates with bronchopulmonary dysplasia, however little is known about its disposition in this population. Methods: We evaluated the pharmacokinetics of dexamethasone in 9 premature neonates with a mean gestational age of 27.3 weeks and a postnatal age of 21.8 days. Results: There was a strong relationship between clearance (4.96 ml·min−1·kg−1) and gestational age (r=0.884). Pharmacokinetic parameters were grouped based on a gestational age of less than 27 weeks (Group I) and greater than 27 weeks (Group II). Mean clearance in group I and group II was 1.69 and 7.57 ml·min−1·kg−1, respectively. Mean distribution volume in group I and II was 1.26 and 2.19 l·kg−1, respectively. No significant relationships were noted between the disposition of dexamethasone and ventilator requirements or adverse effects. Conclusion: The pharmacokinetics of dexamethasone in premature neonates was related to gestational age.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00195934
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  • 3
    Electronic Resource
    Electronic Resource
    Influence of food on the bioavailability and some pharmacokinetic parameters of diprafenone – a novel antiarrhythmic agent (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 315-319 
    Details
    ISSN: 1432-1041
    Keywords: Key words Diprafenone; antiarrhythmics ; bioavailability ; human ; foods ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The present study was done to investigate the effect of food on the bioavailability of diprafenone. Methods: The most important pharmacokinetic parameters (Cmax, t1/2, AUC) and the relative oral availability of a solid oral preparation of racemic diprafenone were investigated when administered to fasting subjects and 10 min after a standard meal, in an open, randomised, crossover trial. Single oral doses of 100 mg were given on two different occasions, at least 1 week apart. The serum concentrations of diprafenone and its hydroxy-metabolite were determined up to 24 hours after administration by a sensitive, specific HPLC method. Fifteen healthy, male volunteers were enrolled in the trial. Their mean height, weight and age were 183 cm, 80 kg and 22 years, respectively. Fourteen volunteers were found to be rapid hydroxylators and one was a slow hydroxylator of debrisoquine. Only data from the rapid hydroxylators were used in the statistical analysis. Results: Food increased the oral bioavailability of diprafenone by approximately 50%. This effect was similar in rapid and in slow hydroxylators. The only slow hydroxylator in this trial had an AUC0–last ratio (with food/fasting) of 1.54. These findings suggest that diprafenone should be administered in a constant temporal relationship to food.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050115
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  • 4
    Electronic Resource
    Electronic Resource
    A single dose of ursodiol does not affect cyclosporine absorption in liver transplant patients (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 335-337 
    Details
    ISSN: 1432-1041
    Keywords: Key words Cyclosporine ; Ursodiol; ursodeoxycholic acid ; absorption ; pharmacokinetics ; liver transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To study the possible influence of ursodiol (ursodeoxycholic acid), a hydrophilic bile acid, on cyclosporine (CsA) bioavailability. Methods: Seven adult liver transplant recipients participated in a randomised cross-over pharmacokinetic study comparing ursodiol (600 mg) with placebo in single doses. Blood concentrations of CsA were measured by HPLC. Results: There was no significant effect of ursodiol on CsA absorption: AUC was 5011 vs 5486 ng⋅h⋅ml–1, Cmax was 832 vs 871 ng⋅ml–1 and tmax was 2 vs 2 h, after ursodiol and placebo, respectively. Conclusion: Although a significant period effect was observed, we conclude that a single dose of ursodiol has little effect on CsA absorption in liver transplant patients and that an interaction in the intestinal lumen between these two drugs is unlikely.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050118
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  • 5
    Electronic Resource
    Electronic Resource
    Absolute bioavailability of fluoride from disodium monofluorophosphate and enteric-coated sodium fluoride tablets (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 321-326 
    Details
    ISSN: 1432-1041
    Keywords: Key words Sodium fluoride ; Disodium monofluorophosphate; absolute bioavailability ; pharmacokinetics ; elderly population
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: The absolute bioavailability and other pharmacokinetic parameters of two fluoride formulations were investigated in 13 healthy volunteers, aged 61–70 years. Methods: The following formulations were administered, under fasting conditions, in a single-dose three-way cross-over design: tablets of 76 mg disodium monofluoro phosphate (MFP, equivalent to 10.0 mg F− ion), enteric-coated (e.c.) tablets of 25 mg sodium fluoride (NaFor, equivalent of 11.3 mg F− ion), and an isoosmotic aqueous injection solution (4 ml) of 22.1 mg sodium fluoride (NaFiv, equivalent of 10.0 mg F− ion). There was a wash-out period of at least one week between each administration. Blood was sampled before and during a 24-hour period after administration. For F− excretion urine was sampled 48 hours before (baseline) and over the 48 hours after the adminstration. Results: The mean t1/2 values of the three formulations were 8.3, 8.7 and 8.3 h for MFP, NaFor and NaFiv respectively, and were not significant different. Mean Cmax after MFP was significantly higher than after NaFor [344 vs 142 μg⋅l−1]. Mean tmax for MFP was shorter than for NaFor [1.1 vs 4.6 h]. MFP had significantly higher bioavailability [102.8%] than NaFor [64.2%]. Conclusion: The MFP formulation showed higher bioavailability with smaller variation than the NaFor formulation. MFP is preferable, therefore, for fluoride therapy in clinical practice, and changing from NaFor to MFP will require adjustment of the dose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050116
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  • 6
    Electronic Resource
    Electronic Resource
    Single oral doses of amisulpride do not enhance the effects of alcohol on the performance and memory of healthy subjects (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 161-166 
    Details
    ISSN: 1432-1041
    Keywords: Key words Amisulpride; ethanol vector ; performance ; memory ; cognitive function ; interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: Amisulpride is a benzamide antipsychotic that binds selectively to dopamine D2- and D3-receptors, preferentially in limbic and hippocampal structures. Since other substituted benzamides have a limited or negligible interaction with alcohol on human performance, amisulpride was studied for this potential. Methods: In a randomised double-blind crossover study, 18 young, non-smoking men took single oral doses of placebo and amisulpride 50 mg and 200 mg, without and with ethanol (0.8 g ⋅kg−1) taken 30 min later. Objective performance tests and self-ratings were done at baseline and 1.5, 3.5 and 6.5 h after drug intake. Memory (immediate and delayed recall) was tested 2 h after dosing. Breath ethanol and the plasma concentrations of amisulpride and prolactin were measured. Three-way ANOVA + Newman-Keul tests were used for statistical analyses; interactions were confirmed by factorial contrast ANOVA. Results: Mean blood ethanol was 0.94, 0.62 and 0.26 g ⋅l−1 at the three test times. It produced significant impairment in all performance tests (symbol digit substitution, simulated driving, body sway, flicker fusion, tapping, nystagmus), reduced both immediate and delayed recall in memory tests, and caused subjective clumsiness, muzziness and mental slowness, mainly between 1.5 to 4.5 h after dosing. Amisulpride, 50 and 200 mg elevated plasma prolactin but had minimal or no effect on performance, attention and memory. The decreases in immediate free recall after the 50 mg dose and in delayed free recall after the 200 mg dose were slight. Amisulpride neither modified blood ethanol concentrations nor enhanced the detrimental effect of ethanol on skilled and cognitive performance; it slightly antagonised ethanol in the digit copying test. Ethanol did not modify the effect of amisulpride on plasma prolactin, and the plasma concentrations of amisulpride were little changed by ethanol. Conclusions: Amisulpride in single oral doses of 50 and 200 mg did not interact significantly with the effects of high, moderate or low concentrations of ethanol on human skilled and cognitive performance. The drugs did interact pharmacokinetically.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050178
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  • 7
    Electronic Resource
    Electronic Resource
    Comparison between concentrations of racemic mefloquine, its separate enantiomers and the carboxylic acid metabolite in whole blood serum and plasma (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 171-173 
    Details
    ISSN: 1432-1041
    Keywords: Key words Mefloquine; mefloquine enantiomers ; carboxylic acid metabolite ; blood concentrations ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To compare concentrations of the separate enantiomers of mefloquine (MQ), total racemic MQ and the carboxylic acid metabolite in different blood fractions at steady state. Setting: Human volunteer laboratory, Unit of Clinical Pharmacology, Karolinska Institute. Volunteers: Ten healthy adult Caucasian volunteers. Methods: Drug concentrations were determined by high-performance liquid chromatography (HPLC). Results: Trough concentrations of the (+)RS enantiomer were higher in venous whole blood than in plasma and serum (mean ratios, 1.41 and 1.38). For the other enantiomer, (−)SR, concentrations were lower in whole blood than in plasma (mean ratio 0.89) and for the metabolite this ratio was 0.5. Conclusion: Stereoselective distribution might be important for antimalarial activity and should be considered when pharmacokinetic studies are performed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050180
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  • 8
    Electronic Resource
    Electronic Resource
    Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 189-193 
    Details
    ISSN: 1432-1041
    Keywords: Key words Dihydropyridine ; Amlodipine ; Grapefruit juice; flavonoids ; interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Objective: This study was performed to assess whether coadminstration with grapefruit juice significantly affects the pharmacokinetics of amlodipine, a dihydropyridine class calcium antagonist with slow absorption, distribution and low plasma clearance. The primary objective was to evaluate whether short exposure to grapefruit juice could affect the metabolism of amlodipine to an extent similar to that previously demonstrated for other dihydropyridines (e.g. felodipine, nisoldipine, nitrendipine). Methods: Twelve healthy male volunteers followed a randomised, open crossover study design, comparing the effect of a single oral dose of amlodipine (5 mg) taken together with a glass of grapefruit juice (250 ml) vs water. Blood samples to determine plasma concentration were taken and blood pressure (BP) and heart rate (HR) were measured throughout the study. Results: When amlodipine was coadministered with grapefruit juice, Cmax was 115% and AUC(0–72 h) was 116% compared with water, but tmax was not significantly changed. There were no significant differences in BP and HR between the two treatments. A small decrease in diastolic BP, however, was observed in both treatments 4–8 h after drug administration, coinciding with Cmax, but this was normalised after 12 h. The BP reduction seen was compensated by a slight increase in HR, which remained throughout the study. Conclusion: An interaction between grapefruit juice and amlodipine was demonstrated. The haemodynamic data showed that a dose of 5 mg was sufficient to achieve a BP reduction in healthy subjects, but the increase in amlodipine plasma concentration seen after intake of grapefruit juice was too small to significantly affect BP or HR. The clinical significance of this food/drug interaction, however, cannot be ignored since there is considerable variation between individuals and a more extensive intake of grapefruit juice might give more pronounced effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050183
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  • 9
    Electronic Resource
    Electronic Resource
    Effects of heat exposure in a Finnish sauna on the pharmacokinetics and metabolism of midazolam (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 335-338 
    Details
    ISSN: 1432-1041
    Keywords: Key words Midazolam ; Sauna; metabolism ; pharmacokinetics ; heat ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The effect of short-term heat exposure in a Finnish sauna on hepatic first-pass metabolism and the capacity to metabolize midazolam were studied in a crossover trial. Midazolam oral (15 mg) and intravenous (0.05 mg ⋅ kg−1) was given to 6 healthy young male volunteers, in random order, during a control session and a sauna bathing session (temperature 85–100° C, relative humidity 25–30%). Blood samples for the determination of plasma midazolam and α-hydroxy midazolam concentrations were taken for 6 h after drug administration. Results: After oral administration, the bioavailability and clearance of midazolam were not affected by sauna bathing, nor was there a significant difference in α-hydroxy midazolam plasma concentration or the α-hydroxy midazolam/midazolam AUC-ratio between the sessions. Midazolam Cmax was increased and its t1/2β was prolonged during the sauna session, but the clinical relevance of the findings appears to be modest. The pharmacokinetics of intravenous midazolam were not affected by sauna bathing. Conclusions: Short-term heat exposure may not affect the first-pass metabolism or hepatic capacity to metabolize midazolam.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050208
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  • 10
    Electronic Resource
    Electronic Resource
    Therapeutic monitoring of nalbuphine: transplacental transfer and estimated pharmacokinetics in the neonate (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 485-489 
    Details
    ISSN: 1432-1041
    Keywords: Key words Nalbuphine ; Neonate; therapeutic drug monitoring ; placental transfer ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Nalbuphine, a mixed agonist-antagonist opiate, is commonly used as a systemic analgesic during labour. Recent reports of perinatal adverse effects prompted us to carry out therapeutic nalbuphine monitoring in obstetric analgesia. Because data on fetomaternal transfer are scarce and the pharmacokinetics of this drug in the neonate are largely unknown, we report data obtained from 28 parturients treated with nalbuphine either intramuscularly and/or intravenously during labour. Plasma nalbuphine levels were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. At delivery, 30–150 min after maternal administration, nalbuphine concentrations ranged from 5.0 to 79.2 ng ⋅ ml−1 in mother plasma samples and from 3.0 to 46.6 ng ⋅ ml−1 in umbilical cord plasma samples. Nalbuphine concentrations were highly correlated to dose. The fetomaternal ratio was high: 0.74 and not correlated to the administered dose of nalbuphine. An estimated plasma half-life of 4.1 h was calculated from two determinations in the neonate based on the assumption of a monoexponential decay of nalbuphine concentrations. Apart from a flattening of the fetal heart rate tracing in 54% of the cases, only one neonate had a low Apgar score at birth. The apparent prolonged half-life of nalbuphine in the neonate indicates the usefulness of an intramuscular injection of naloxone to prevent recurrence of cardiorespiratory depression due to nalbuphine administration to the mother.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050054
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  • 11
    Electronic Resource
    Electronic Resource
    Bioavailability of 1-deamino-8-D-arginine vasopressin with an enzyme inhibitor (aprotinin) from the small intestine in healthy volunteers (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 491-495 
    Details
    ISSN: 1432-1041
    Keywords: Key words Aprotinin ; Arginine vasopressin; bioavailability ; dDAVP ; enzyme inhibitor ; gastrointestinal tract ; healthy volunteer ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP), with and without an enzyme inhibitor, was studied in six healthy, male volunteers aged 19–34 years, followed for 8 h after each drug administration. Methods: For i.v. administration the subjects received 4 μg dDAVP. For intestinal administration 500 μg dDAVP was administered directly, in two separate sessions, in the first part of the duodenum via a triple-lumen channel tube. In one session a solution of isotonic polyethylene glycol (PEG) was given as a continuous enteral perfusion. In the other session a solution of PEG and aprotinin was administered enterally at the constant rate of 5 ml⋅min−1 for 4 h. Plasma dDAVP was measured using a specific, sensitive radioimmunoassay and intestinal juice was collected for measurement of lipase, chymotrypsin and pH every 30 min for 5 h. Results: The intestinal chymotrypsin activity was decreased after perfusion of aprotinin while the lipase activity was not modified. After i.v. administration, the half-life of elimination of dDAVP was 1.56 h and plasma clearance 1.24 ml⋅min⋅kg−1. The mean bioavailability after duodenal administration of dDAVP + aprotinin was 0.46% compared with 0.09% after duodenal administration of dDAVP alone. The bioavailability of dDAVP after direct duodenal administration of an aqueous solution was similar to that after swallowing a tablet in a previous study and increased 5 times when given together with a perfusion of an enzyme inhibitor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050146
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  • 12
    Electronic Resource
    Electronic Resource
    Multiple dose pharmacokinetics of tiludronate in healthy volunteers (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 175-181 
    Details
    ISSN: 1432-1041
    Keywords: Key words Tiludronate; healthy volunteers ; bisphosphonates ; pharmacokinetics ; calcium metabolism ; bone resorption ; adverse events
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: A double-blind, placebo-controlled study was conducted to assess the pharmacokinetics and pharmacodynamics of the bisphosphonate tiludronic acid, administered once daily as sodium tiludronate 200, 400, 600 and 800 mg for 12 days. Four groups of ten subjects participated in the study, with a drug to placebo ratio of 4:1. Methods: Pre-dose blood samples were taken on alternate days, starting on Day 1 and additional samples were collected over 144 h following the final dose on Day 12. Urine was collected over 24 h after the final dose. Indices of calcium homeostasis and biochemical markers of bone turnover were assessed during the study as pharmacodynamic parameters. Tolerability was evaluated with special emphasis on renal function and gastrointestinal irritation. Adverse experiences were assessed at regular time intervals. Results and conclusions: Steady state was attained from Day 4 (200 mg) or from Day 6 (400, 600 and 800 mg). Following the final dose on Day 12, minimal plasma concentrations (Cmin) ranged between 0.19 and 1.5 mg ⋅ l−1, and maximal plasma concentrations (Cmax) between 1.1 and 7.8 mg⋅l−1 for the lowest and highest doses, respectively. A supra-proportional increase in Cmax, AUC24 and Ae 24 with dose was observed. There was a linear relationship between the plasma tiludronic acid and its urinary excretion rate, so, the disproportional rise in Cmax and AUC24 with increasing dose could not be attributed to saturation of renal excretion. Certain indices of calcium homeostasis changed significantly during the study, but generally, became only prominent at the highest dose level of 800 mg. Total serum calcium and the urinary calcium/creatinine clearance ratio fell, indicating depression of osteoclastic bone resorption, which was not revealed by serum osteocalcin levels probably because of the brevity of the treatment (12 days). In response to the decline in serum calcium, serum 1,25-dihydroxyvitamin D3 and intact PTH (1–84) levels increased. None of the safety parameters raised any concerns about the safety of sodium tiludronate administered in this way.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050181
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  • 13
    Electronic Resource
    Electronic Resource
    Haemodynamic effects and pharmacokinetics of oral d-and l-nebivolol in hypertensive patients (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 259-264 
    Details
    ISSN: 1432-1041
    Keywords: Key words Nebivolol ; Hypertension; d ; l-enantiomers ; pharmacokinetics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Nebivolol is a selective β1-adrenergic receptor blocker possessing an ancillary vasodilating effect. The objective of the present study was to study the haemodynamic and pharmacokinetic properties of nebivolol 5 mg once daily in a double-blind, placebo-controlled cross-over study. Methods: Fifteen patients, 12 men and 3 women, with essential hypertension were investigated. Blood pressure and peripheral circulation were determined after acute oral nebivolol administration, 5 mg daily, and after 4 weeks treatment. Results: The acute effect on blood pressure upon single-dosing was weak and non-significant. After 4 weeks both systolic blood pressure (152 vs 163 mmHg) and diastolic blood pressure (89 vs 97 mmHg) were significantly reduced after nebivolol treatment as compared to placebo. Following the first dose the venous volume was higher on placebo (5.88 ml ⋅ 100 ml−1 tissue) as compared to active nebivolol treatment (5.17 ml ⋅ 100 ml−1 tissue), while there were no statistically significant differences with regard to venous plethysmographic findings after 1 month on placebo (5.53 ml ⋅ 100 ml−1 tissue) or on active treatment (5.97 ml ⋅ 100 ml−1 tissue). Calculated peripheral resistance did not differ between active treatment (617 units) or placebo (548 units) after the first dose, whereas it was significantly lowered after 4 weeks of nebivolol treatment (483 units) as compared to placebo (593 units). Conclusions: Oral nebivolol 5 mg once daily lowered blood pressure and heart rate during steady state compared to placebo. Moreover, venous volume was reduced during acute but not steady-state dosing, while peripheral resistance was unaffected in the acute phase but reduced during steady state. Plasma concentrations of the separate enantiomers plus hydroxylated metabolites after the first and last dose in hypertensive patients were similar to those in healthy subjects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050194
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  • 14
    Electronic Resource
    Electronic Resource
    Lack of pharmacodynamic and pharmacokinetic interaction between pantoprazole and phenprocoumon in man (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 277-281 
    Details
    ISSN: 1432-1041
    Keywords: Key words Pantoprazole; Proton pump inhibitor drug interaction ; oral anticoagulant phenprocoumon ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Pantoprazole is a selective proton pump inhibitor characterized by a low potential to interact with the cytochrome P450 enzymes in man. Due to the clinical importance of an interaction with anticoagulants, this study was carried out to investigate the possible influence of pantoprazole on the pharmacodynamics and pharmacokinetics of phenprocoumon. Methods: Sixteen healthy male subjects were given individually adjusted doses of phenprocoumon to reduce prothrombin time ratio (Quick method) to about 30–40% of normal within the first 5–9 days and to maintain this level. The individual maintenance doses remained unaltered from day 9 on and were administered until day 15. Additionally, on study days 11–15, pantoprazole 40 mg was given per once daily. As a pharmacodynamic parameter, the prothrombin time ratio was determined on days 9 and 10 (reference value) and on days 14 and 15 (test value), and the ratio test/reference was evaluated according to equivalence criteria. Results: The equivalence ratio (test/reference) for prothrombin time ratio was 1.02 (90% confidence interval 0.95–1.09), thus fulfilling predetermined bioequivalence criteria (0.70–1.43). The pharmacokinetic characteristics AUC0–24h and Cmax of S(−)-and R(+)-phenprocoumon were also investigated using equivalence criteria. Equivalence ratios and confidence limits of AUC0–24h and of Cmax of S(−)-phenprocoumon (0.93, 0.87–1.00 for AUC0–24h; 0.95, 0.88–1.03 for Cmax) and of R(+)-phenprocoumon (0.89, 0.82–0.96; 0.9, 0.83–0.98) were within the accepted range of 0.8–1.25. Conclusion: Pantoprazole does not interact with the anticoagulant phenprocoumon on a pharmacodynamic or pharmacokinetic level. Concomitant treatment was well tolerated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050198
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  • 15
    Electronic Resource
    Electronic Resource
    Bioavailability of estradiol from a new matrix and a conventional reservoir-type transdermal therapeutic system (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 327-330 
    Details
    ISSN: 1432-1041
    Keywords: Key words Hormone replacement therapy; estradiol ; pharmacokinetics ; bioequivalence ; postmenopausal volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Bioavailability of estradiol delivered from a newly developed matrix-type transdermal therapeutic system (MTTS) was compared with that of the conventional reservoir-type system (RTTS). Both formulations have a nominal delivery rate of 50 μg per day of 17β-estradiol (E2). Plasma concentrations of E2 and estrone (E1) were determined at steady state during a 96-h application of each formulation to 34 postmenopausal volunteers, using a two-stage randomized two-period crossover design. Results: The MTTS proved to be equivalent to the RTTS with respect to the extent of E2 absorption. Due to differences in patch design and composition, the rate of absorption was different between the two systems, with less fluctuating E2 plasma levels during application of the matrix system. Local tolerability and adhesion of MTTS appeared to be better than those of the reservoir system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050206
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  • 16
    Electronic Resource
    Electronic Resource
    Rectal pharmacokinetics of budesonide (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 293-298 
    Details
    ISSN: 1432-1041
    Keywords: Key words Budesonide; enema ; pharmacokinetics ; healthy subjects ; hepatic bypass
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and systemic availability of budesonide after rectal administration of two single enema doses (2 mg in 100 ml fluid of almost identical composition) were compared in 15 healthy volunteers. In 11 of these subjects, 2 mg oral budesonide in a gelatine capsule was given on a separate occasion. An intravenous administration (0.5 mg) was given as reference. With this design, individual hepatic bypass of the rectally administered budesonide dose could be estimated. The pharmacokinetics of the two enema formulations were similar, although not bioequivalent. Mean systemic availability was 16% (range 4.2–43%) and 15% (3.2–50%) after rectal administration and 6.3% (2.4–10%) after oral administration. The rectal data revealed a small intra- but a substantial inter-subject variability in systemic availability. Cmax was 3.3 nmol ⋅ l−1 (0.95–8.2), 3.0 nmol ⋅ l−1 (0.64–8.9) and 1.3 nmol ⋅ l−1 (0.61–3.0), respectively, for the three formulations. Absorption was rapid and essentially terminated within 3 h after rectal dosing [tmax = 1.3 h for both formulations (range 0.5–2.0)], but was slower after oral dosing [tmax = 2.1 h (1.0–6.0)]. If a complete absorption after oral and rectal dosing is assumed, the fraction of the rectal dose entering the liver at first pass can be calculated to be 88% (55–99%). The higher systemic availability and intersubject variability after rectal dosing does not seem to be caused by differences in first-pass liver metabolism but rather by hepatic bypass of a varying portion of administered drug. This portion seems to be typical for an individual and might be explained by anatomical differences between subjects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00226330
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  • 17
    Electronic Resource
    Electronic Resource
    Design of a suitable formulation of FK613, a novel antiallergic agent, based on its pharmacokinetic and pharmacodynamic properties in healthy subjects (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 279-284 
    Details
    ISSN: 1432-1041
    Keywords: Antiallergic drug ; FK613 ; pharmacokinetics ; histamine skin-test ; drug formulation ; urinary excretion ; safety
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetic and pharmacodynamic properties of FK613, a novel indolyl piperidine derivative, were investigated after oral administrations of 5, 10 and 20 mg in hard gelatin capsules to healthy male volunteers. FK613 was rapidly and almost completely absorbed, and 〉89% was recovered in the urine as the unchanged form. The urinary excretion of FK613 was linearly correlated with plasma concentration and its low water solubility was the main concern regarding the safety. In another experiment using a double-blind crossover design, in which 0 (placebo), 5 and 20 mg FK613 were administered to determine the plasma concentration-effect relationship, suppression of the intradermal histamine-induced skin reaction by FK613 was observed. Thus, the maintenance of a plasma concentration of FK613 in the range of 80–250 ng · ml-1 was recommended to ensure the suppression of histamine-induced wheal by 〉50% and not to exceed the solubility in urine. To achieve this, a new hydrogel-type formulation of FK613 was developed, with the aim both of delaying its absorption, so as to suppress the sharp rise in plasma concentration, and of maintaining the effective concentration for a longer period of time. This formulation was administered after meals at the doses of 20, 30, 40, 50 and 60 mg, and at repeated doses of 40 mg twice daily for 6.5 days to evaluate the pharmacokinetics and safety in healthy subjects. The area under the plasma concentration curve increased linearly with dose, whereas maximum plasma concentration (Cmax) tended to peak as dose increased, indicating the desirable properties of this formulation. Although Cmax exceeded 250 ng/ml at doses of 30 mg or more, no urinary crystal formation was observed on careful inspection of urine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00226328
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  • 18
    Electronic Resource
    Electronic Resource
    Rectal pharmacokinetics of budesonide (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 293-298 
    Details
    ISSN: 1432-1041
    Keywords: Budesonide ; enema ; pharmacokinetics ; healthy subjects ; hepatic bypass
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and systemic availability of budesonide after rectal administration of two single enema doses (2 mg in 100 ml fluid of almost identical composition) were compared in 15 healthy volunteers. In 11 of these subjects, 2 mg oral budesonide in a gelatine capsule was given on a separate occasion. An intravenous administration (0.5 mg) was given as reference. With this design, individual hepatic bypass of the rectally administered budesonide dose could be estimated. The pharmacokinetics of the two enema formulations were similar, although not bioequivalent. Mean systemic availability was 16% (range 4.2–43%) and 15% (3.2–50%) after rectal administration and 6.3% (2.4–10%) after oral administration. The rectal data revealed a small intra- but a substantial inter-subject variability in systemic availability. Cmax was 3.3 nmol·l-1 (0.95–8.2), 3.0 nmol·l-1 (0.64–8.9) and 1.3 nmol·l-1 (0.61–3.0), respectively, for the three formulations. Absorption was rapid and essentially terminated within 3 h after rectal dosing [tmax=1.3 h for both formulations (range 0.5–2.0)], but was slower after oral dosing [tmax=2.1 h (1.0–6.0)]. If a complete absorption after oral and rectal dosing is assumed, the fraction of the rectal dose entering the liver at first pass can be calculated to be 88% (55–99%). The higher systemic availability and intersubject variability after rectal dosing does not seem to be caused by differences in first-pass liver metabolism but rather by hepatic bypass of a varying portion of administered drug. This portion seems to be typical for an individual and might be explained by anatomical differences between subjects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00226330
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  • 19
    Electronic Resource
    Electronic Resource
    Increase in magnesium plasma level after orally administered trimagnesium dicitrate (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 317-323 
    Details
    ISSN: 1432-1041
    Keywords: Magnesium ; Plasma level ; pharmacokinetics ; bioavailability ; circadian fluctuation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Magnesium plasma concentrations were measured in healthy probands before and after administration of trimagnesium dicitrate by the oral and intravenous routes. There was a notable circadian fluctuation of the plasma concentration with a peak in the evening hours. After oral administration of 12 and 24 mmol magnesium, a long-lasting, statistically significant increase in plasma magnesium concentration measured as the increase in area under the curve (AUC) between 0 and 12 h, of 3.1% and 4.6%, respectively, was found. After intravenous administration of 4 and 8 mmol magnesium, AUCs increased by 9.5% and 16.1%, respectively. The decline in the plasma magnesium concentration after i.v. administration was compatible with a three-compartment model with a terminal half-time of about 8 h. Although no absolute value of the oral bioavailability of trimagnesium dicitrate could be determined from the data, our results may be important in helping to elucidate the influence of magnesium preparations on the plasma magnesium concentration. By comparing the effects of different preparations, it should be possible to estimate the relative oral bioavailability and the bioequivalence of these preparations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00226334
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  • 20
    Electronic Resource
    Electronic Resource
    Multiple-dose clinical pharmacology of the catechol-O-methyl-transferase inhibitor tolcapone in elderly subjects (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 47-55 
    Details
    ISSN: 1432-1041
    Keywords: Key words Tolcapone ; Elderly; levodopa ; pharmacokinetics ; pharmacodynamics ; multiple-dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Objective: The purpose of this study was to assess the multiple-dose clinical pharmacology of tolcapone, a novel catechol-O-methyltransferase (COMT) inhibitor, in elderly subjects. Methods: The drug was administered orally t.i.d. for 7 days to four sequential groups of eight elderly subjects (gender ratio1:1) at doses of 100, 200, 400 and 800 mg in a double-blind, randomised, placebo-controlled, ascending-multiple-dose design. On days 2 and 7, a single dose of levodopa/benserazide 100/25 mg was given 1 h after the first intake of tolcapone. Plasma concentrations of tolcapone, its metabolite 3-O-methyltolcapone, levodopa and 3-O-methyldopa were determined during the course of the study in conjunction with COMT activity in erythrocytes. Results: Tolcapone was well tolerated at all dose levels, with a slight increase in gastrointestinal adverse events in females at higher doses. The drug was rapidly absorbed and eliminated and showed no changes in pharmacokinetics with time during multiple doses of 100 and 200 mg t.i.d. At doses of 400 and 800 mg t.i.d., tolcapone accumulated moderately as reflected in increased Cmax and AUC values. Despite the long half-life of 3-O-methyltolcapone (39 h), only minor accumulation occurred due to suppression of its formation by tolcapone. The pharmacodynamics of tolcapone did not change during the week of treatment as reflected in inhibition of COMT activity in erythrocytes, the derived parameters of the plasma concentration-effect relationship (inhibitory Emax model with constant EC50 values) and the effect on levodopa pharmacokinetics (1.6 to 2.5-fold increase in bioavailability). This suggests the absence of tolerance development and the insignificance of the altered pharmacokinetics at 400 and 800 mg t.i.d. with regard to the pharmacodynamics. Conclusion: The results of this study offer promising perspectives for the application of tolcapone as adjunct therapy to levodopa in the treatment of Parkinson’s disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050068
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  • 21
    Electronic Resource
    Electronic Resource
    A comparison of the pharmacokinetics and pharmacodynamics of cilazapril between Chinese and Caucasian healthy, normotensive volunteers (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 57-62 
    Details
    ISSN: 1432-1041
    Keywords: Key words Cilazapril ; Caucasians ; Chinese; cilazaprilat ; pharmacokinetics ; pharmacodynamics ; ACE inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Methods: The pharmacokinetics and pharmacodynamics of the angiotensin converting enzyme (ACE) inhibitor cilazapril were studied in 12 Chinese and 13 Caucasian, healthy, normotensive volunteers on their normal diet. Cilazapril was given orally as a single 2.5 mg capsule. Plasma was sampled for assay of the active metabolite, cilazaprilat, plasma renin activity (PRA), aldosterone, angiotensin I (AI) and ACE-activity. Plasma concentrations of the active drug were measured by radioimmunoassay. Blood pressure and heart rate were measured at regular intervals. Results: The pharmacokinetic parameters of cilazaprilat were similar in the two ethnic groups. No significant difference in plasma concentrations was found at any of the time points. However, the weight-adjusted plasma clearance was significantly higher in the Chinese group, which is compatible with their lower body weight. The effects on plasma hormones were also comparable, although there was a somewhat greater rise in PRA and greater fall in aldosterone levels in Chinese than in Caucasians. The effect of cilazapril on blood pressure and heart rate was greater than was previously reported in healthy volunteers. Systolic (SBP) and diastolic (DBP) blood pressure were significantly reduced in both groups, but there was a more prolonged reduction in DBP in Caucasians. In addition, heart rate (HR) was significantly increased from baseline from 5 h onwards in Chinese subjects and significantly higher in comparison with Caucasians at most time points from 1.5 h onwards. The pharmacokinetic parameters of cilazapril were essentially the same in healthy, normotensive Chinese and Caucasians. Cilazapril reduced blood pressure acutely in both groups, with good tolerance. The inhibition of ACE in relationship to time and the plasma concentrations of cilazaprilat were similar in the two groups, although the changes in PRA and aldosterone suggest an ethnic difference in the responses of the renin-angiotensin-aldosterone system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050069
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  • 22
    Electronic Resource
    Electronic Resource
    Pharmacokinetic interaction between cyclosporine and the dihydropyridine calcium antagonist felodipine (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 203-208 
    Details
    ISSN: 1432-1041
    Keywords: Key words Cyclosporine ; Felodipine; dehydrofelodi-pine ; pharmacokinetics ; blood pressure ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: In a double blind, randomised, placebo-controlled, cross-over study 12 healthy male volunteers were allocated to receive felodipine + placebo, cyclosporine + placebo, and felodipine + cyclosporine in order to investigate the interaction between the calcium channel blocker felodipine and cyclosporine as it affects the pharmacokinetics of felodipine, dehydrofelodipine, and cyclosporine, and 24-hour blood pressure measurements. Methods: Single doses of cyclosporine (capsules, 5 mg/kg body weight) and of felodipine (extended release (ER) tablets 10 mg) were given at a 1–2 week interval. Plasma drug concentrations were followed for 2 days after drug intake. Results: For cyclosporine, Cmax was increased after combined treatment (16%) compared to cyclosporine alone, but felodipine did not influence other kinetic parameters of cyclosporine. For felodipine, combined treatment with cyclosporine and felodipine increased AUC and Cmax (58% and 151%, respectively) and lowered mean residence time (24%) significantly compared to felodipine alone. For the metabolite dehydrofelodipine, too, AUC and Cmax were increased after the combined treatment (43% and 94%, respectively). Mean 24-hour systolic and diastolic blood pressures were significantly lower after felodipine, both when felodipine was given alone (121/68 mmHg) and in combination with cyclosporine (122/68 mmHg) compared to cyclosporine alone (127/73 mmHg). Conclusion: A combined single dose of cyclosporine and felodipine in healthy subjects increased the AUC and Cmax of felodipine suggesting a cyclosporine-induced decrease in the first-pass metabolism of felodipine, whereas the AUC of cyclosporine was only slightly increased by felodipine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050093
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  • 23
    Electronic Resource
    Electronic Resource
    Effect of food on the bioavailability of oxybutynin from a controlled release tablet (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 221-223 
    Details
    ISSN: 1432-1041
    Keywords: Key words Oxybutynin; effect of food ; N-desethyl oxybutynin ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The effect of food on the bioavailability of oxybutynin was assessed in a randomised cross-over study in 23 healthy volunteers. A single oral 10 mg dose of a controlled release oxybutynin tablet was administered after a high fat breakfast and to fasting subjects. The AUC, Cmax, tmax, t1/2 and MRT of oxybutynin and its active metabolite N-desethyloxybutynin were determined. Results: Breakfast did not change the AUC of oxybutynin but increased the AUC of N-desethyloxybutynin by about 20% . The Cmax of oxybutynin and N-desethyl oxybutynin were two-fold higher when the drug was administered after breakfast compared to the fasting state. Conclusion: Breakfast significantly reduced the MRT of oxybutynin and N-desethyloxybutynin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050096
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  • 24
    Electronic Resource
    Electronic Resource
    Stereoselective pharmacokinetics of mefloquine in young children (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 241-244 
    Details
    ISSN: 1432-1041
    Keywords: Key words Mefloquine ; Children; enantiomer ; pharmacokinetics ; stereoselectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: the stereospecificity of mefloquine pharmacokinetics in children has been investigated. Patients: Twelve children aged 6 to 24 months were treated for uncomplicated falciparum malaria with a single oral dose of 25 mg⋅kg−1 racemic mefloquine in combination with sulfadoxine and pyrimethamine. Methods: concentrations of mefloquine enantiomers were determined using a coupled achiral-chiral chromatographic system. Pharmacokinetic parameters were calculated using model-independent analysis. Results: Maximum plasma concentrations, areas under the curve and apparent plasma elimination half-lives were higher for the (−) enantiomer than its antipode. In contrast, the apparent volume of distribution (V/f) and total clearance (Cl/f) values were higher for the (+) enantiomer. Conclusion: the stereoselectivity of mefloquine pharmacokinetics is similar to that observed in adults.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050100
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  • 25
    Electronic Resource
    Electronic Resource
    Effect of itraconazole on the pharmacokinetics and pharmacodynamics of zopiclone (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 331-334 
    Details
    ISSN: 1432-1041
    Keywords: Key words Zopiclone ; Itraconazole; drug interaction ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: We studied the possible interaction between itraconazole, a potent inhibitor of CYP3A, and zopiclone, a short-acting hypnotic. Methods: A double-blind, randomized, two-phase crossover design was used. Ten healthy young subjects received daily either 200 mg itraconazole or placebo for 4 days. On day 4 they ingested a single 7.5-mg oral dose of zopiclone. Plasma concentrations of zopiclone and itraconazole were determined and pharmacodynamic responses were measured up to 17 h. Results: Itraconazole significantly increased the Cmax of zopiclone from 49 to 63 ng ⋅ ml−1. The t1/2 of zopiclone was prolonged from 5.0 to 7.0 h. The AUC(0–∞) of zopiclone was increased from 415 to 719 ng ⋅ ml−1 h by itraconazole. No statistically significant differences were observed in the pharmacodynamic responses between the groups. Conclusion: Itraconazole has a statistically significant pharmacokinetic interaction with zopiclone but this is only of limited clinical importance, at least in young adults.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050207
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  • 26
    Electronic Resource
    Electronic Resource
    Influence of age, frailty and liver function on the pharmacokinetics of brofaromine (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 387-391 
    Details
    ISSN: 1432-1041
    Keywords: Key words Liver function tests; elderly ; pharmacokinetics ; geriatrics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66–92 y) and 12 healthy volunteers (20–35 y). Methods: Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance). Results: In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 μmol*h⋅l−1, clearance was reduced (5.0 vs. 11.8 l⋅h−1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r = 0.41, P = 0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r = 0.94, P 〈 0.0001). Conclusion: Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050037
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  • 27
    Electronic Resource
    Electronic Resource
    Influence of age, frailty and liver function on the pharmacokinetics of brofaromine (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 387-391 
    Details
    ISSN: 1432-1041
    Keywords: Liver function tests ; elderly ; pharmacokinetics ; geriatrics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66–92 y) and 12 healthy volunteers (20–35 y). Methods: Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance). Results: In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 μmol*h·l−1, clearance was reduced (5.0 vs. 11.8 l·h−1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r=0.41, P=0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r=0.94, P〈0.0001). Conclusion: Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00203783
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  • 28
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous injection of increasing doses (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 411-415 
    Details
    ISSN: 1432-1041
    Keywords: Moxisylyte ; pharmacokinetics ; intracavernous administration ; healthy volunteers ; adverse events ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The concentration-time profiles of specific metabolites of moxisylyte, an α-adrenoceptor blocking agent, in the plasma and urine from 18 healthy volunteers were investigated after intracavernous (IC) administrations at three dose levels (10, 20 and 30 mg). Results: Four metabolites, unconjugated desacetyl-moxisylyte (DAM), DAM glucuronide, and DAM and monodesmethylated DAM (MDAM) sulphates were found in plasma and urine. For all metabolites, t1/2 elimination was independent of the administered dose (1.19 h for unconjugated DAM; 1.51 h for DAM glucuronide; 1.51 h for DAM sulphate; and 2.17 h for MDAM sulphate). Cmax and AUC increased in direct proportion to dose, except for the inactive DAM glucuronide. Any the differences detected were small and equivalence of the three doses can be accepted. Conclusion: The pharmacokinetics of moxisylyte in humans following intracavernous administration were linear in the dose range 10 to 30 mg.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00203788
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  • 29
    Electronic Resource
    Electronic Resource
    Therapeutic monitoring of nalbuphine: transplacental transfer and estimated pharmacokinetics in the neonate (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 485-489 
    Details
    ISSN: 1432-1041
    Keywords: Nalbuphine ; Neonate ; therapeutic drug monitoring ; placental transfer ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Nalbuphine, a mixed agonist-antagonist opiate, is commonly used as a systemic analgesic during labour. Recent reports of perinatal adverse effects prompted us to carry out therapeutic nalbuphine monitoring in obstetric analgesia. Because data on fetomaternal transfer are scarce and the pharmacokinetics of this drug in the neonate are largely unknown, we report data obtained from 28 parturients treated with nalbuphine either intramuscularly and/or intravenously during labour. Plasma nalbuphine levels were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. At delivery, 30–150 min after maternal administration, nalbuphine concentrations ranged from 5.0 to 79.2 ng·ml−1 in mother plasma samples and from 3.0 to 46.6 ng·ml−1 in umbilical cord plasma samples. Nalbuphine concentrations were highly correlated to dose. The fetomaternal ratio was high: 0.74 and not correlated to the administered dose of nalbuphine. An estimated plasma half-life of 4.1 h was calculated from two determinations in the neonate based on the assumption of a monoexponential decay of nalbuphine concentrations. Apart from a flattening of the fetal heart rate tracing in 54% of the cases, only one neonate had a low Apgar score at birth. The apparent prolonged half-life of nalbuphine in the neonate indicates the usefulness of an intramuscular injection of naloxone to prevent recurrence of cardiorespiratory depression due to nalbuphine administration to the mother.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00195935
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  • 30
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of quinine in patients with chronic renal failure (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 497-501 
    Details
    ISSN: 1432-1041
    Keywords: Quinine ; Malaria ; pharmacokinetics ; chronic renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Methods: We investigated the pharmacokinetics of quinine (Qn) following administration of a single oral dose of 600 mg Qn sulphate in six male Thai patients with a moderate degree of chronic renal failure (CRF), and six male Thai subjects with normal renal function. Results: The drug was well tolerated in both groups of subjects; no major adverse reactions were observed. A marked alteration in the pharmacokinetics of Qn was found in patients with CRF compared to healthy subjects; there were six signifiicant changes in the pharmacokinetic parameters. Absorption was delayed, but increased in CRF (tmax 4.5 vs 1.6 h, Cmax 6.17 vs 3.45 μg·ml−1). Total clearance was significantly reduced 0.94 vs 2.84 ml·min−1·kg−1, whereas Vz/f remained unchanged (1.82 vs 2.78 1·kg−1). This resulted in the increased values of AUC and prolongation of the t1/2z and MRT in the patients (AUC 181.5 vs 61.8 μg·min−1·ml−1, t1/2z 26 vs 9.7 h, MRT 36.4 vs 11.3 h). Median concentrations of plasma unbound fraction of Qn collected at 4 h after drug administration in patients and healthy subjects were 7.3 vs 9.8%, respectively.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00195937
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  • 31
    Electronic Resource
    Electronic Resource
    Evaluation of plasma and urinary salbutamol levels in COPD (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 91-93 
    Details
    ISSN: 1432-1041
    Keywords: Key words Salbutamol; nebulised ; pharmacokinetics ; COPD ; overnight urinary salbutamol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To evaluate the use of trough plasma salbutamol and overnight urinary salbutamol excretion in the assessment of nebulised salbutamol delivery in patients with chronic obstructive pulmonary disease (COPD). Methods: Twenty in-patients with COPD receiving nebulised salbutamol, age 69.7 years, FEV1 38.1% predicted, were studied on two consecutive days, receiving four 2.5 mg doses of nebulised salbutamol on day 1 and four 5 mg doses of nebulised salbutamol on day 2, the first dose at 8.00 h the last dose at 22.00 h. Salbutamol delivery was assessed after the last dose by trough plasma salbutamol 8.00 h and overnight urinary excretion of salbutamol (22.00–8.00 h). Results: Levels of urinary salbutamol were detectable in all 20 patients at both doses, whereas for plasma salbutamol detectable levels were only found in 16/20 cases at the 2.5 mg dose and in all cases at the 5 mg dose. For overnight urinary salbutamol (μg⋅10 h−1  n = 20) the results were 141 for 2.5 mg and 249 for 5 mg. The dose ratio for urinary salbutamol between 2.5 mg and 5 mg doses was 1.83. Results for plasma salbutamol (ng/ml, n = 16) were 1.58 at 2.5 mg and 2.43 at 5 mg: dose ratio (geometric mean) 1.49. Conclusion: Overnight urinary salbutamol provides a simple and effective measure of nebulised salbutamol delivery in patients with COPD, which would be suitable for studying nebuliser performance and compliance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050166
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  • 32
    Electronic Resource
    Electronic Resource
    Plasma concentrations and pharmacokinetics of idebenone and its metabolites following single and repeated doses in young patients with mitochondrial encephalomyopathy (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 167-169 
    Details
    ISSN: 1432-1041
    Keywords: Key words Idebenone; mitochondrial encephalomyopathy ; young patients ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics and tolerance of idebenone after single or repeated doses have been studied in young patients with mitochondrial encephalomyopathy. Results: No significant adverse effects were noted. In 3 out of 7 patients idebenone induced overall stimulation and improvement in arousal. Plasma concentrations of idebenone and its main metabolites were determined and the pharmacokinetic parameters of idebenone after single and repeated doses were estimated. During the single dose study, the mean plasma concentrations of idebenone and its main metabolites and mean pharmacokinetic parameters were comparable to published results (Cmax = 452.2 ng ⋅ ml−1, tmax = 2.3 h, AUC = 26 μg ⋅ ml−1 ⋅ h, t1/2β = 16.5 h). During the repeated doses study, no significant difference was found between mean residual plasma concentrations of idebenone on Day 2 (47 ng ⋅ ml−1) and Day 5 (70.6 ng ⋅ ml−1), and mean t1/2β of idebenone after the single and after repeated dose studies, i.e., there was no evidence of accumulation. Although idebenone did not appear to accumulate during this study, the coadministration of anticonvulsants, often prescribed during mitochondrial encephalomyopathy, can affect its pharmacokinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050179
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  • 33
    Electronic Resource
    Electronic Resource
    Macromolecular Carrier Systems for Targeted Drug Delivery: Pharmacokinetic Considerations on Biodistribution (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 820-831 
    Details
    ISSN: 1573-904X
    Keywords: macromolecular carrier ; pharmacokinetics ; targeting ; protein drugs ; gene medicines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract This review article describes the current status and future perspectives of site-specific drug delivery by means of macromolecular carrier systems. Basic aspects and recent advances of targeted delivery of 1) conventional drugs, 2) protein drugs, and 3) gene medicines including antisense oligonucleotides and plasmid DNA, are reviewed from a pharmacokintic perspective. Successful in vivo application of macromolecular carrier systems requires pharmacokinetic considerations at whole body, organ, cellular and subcellular levels. The integration of simultaneous research progress in the multidisciplinary fields such as biochemistry, cell and molecular biology, pharmacology, and pharmacokinetics will accelerate the emergence of marketed drugs with macromolecular carrier systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016084508097
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  • 34
    Electronic Resource
    Electronic Resource
    Targeted Delivery of Doxorubicin via Sterically Stabilized Immunoliposomes: Pharmacokinetics and Biodistribution in Tumor-bearing Mice (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 861-868 
    Details
    ISSN: 1573-904X
    Keywords: sterically stabilized immunoliposomes ; targeting ; doxorubicin ; lung metastases ; pharmacokinetics ; biodistribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate benefits in tumor localization, availability, and noncancerous organ distribution of doxorubicin (DOX) delivered via small (≤120 nm) sterically stabilized immunoliposomes targeted against a tumor-associated antigen in fibrosarcoma-bearing mice. Methods. DOX-loaded liposomes were prepared with (i) specific monoclonal IgG3 antibody (32/2, D-SSIL-32/2); (ii) non-specific IgG3 (D-SSIL-IgG); or (iii) no IgG (D-SSL) on their surface. Equal DOX amounts were injected intravenously via each type of liposome into BALB/c mice carrying experimental lung metastases of a polyoma virus-induced fibrosarcoma (A9 etc 220) expressing a polyoma virus-induced tumor-associated antigen (PAA) on their surface. Metastases occurred mainly in lung. Mice were treated at 3 stages of tumor development (micrometastases, medium-size metastases, and large, necrotic metastases). Performance evaluation was based on time-dependent quantification of DOX and DOX metabolites (DOX-M) in lung tumor, noncancerous organs, and plasma. Results. (i) DOX delivered via both SSIL retained the prolonged circulation time typical of DOX delivered via D-SSL. (ii) DOX accumulation in noncancerous organs was similar for all preparations. Low levels of DOX-M were obtained for all three preparations in all organs except liver, suggesting a similar processing, (iii) Preparations differed in behavior in lung tumor depending on tumor size and microanatomy. Only at the micrometastases stage were the specifically targeted D-SSIL-32/2 superior to D-SSL and D-SSIL-IgG, delivering 2–4 times more drug into the tumor, (iv) DOX-M level in all three tumor stages was in the following order: D-SSIL-32/2 〉〉 D-SSL 〉〉 D-SSIL-IgG, suggesting that DOX delivered as D-SSIL-32/2 is most available to tumor cells. Conclusions. The advantage of specific targeting of sterically stabilized liposomes is expressed mainly in increasing availability of DOX to tumor cells in a way which is dependent on tumor microanatomy. The impact of this advantage to therapeutic efficacy remains to be determined.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016096910822
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  • 35
    Electronic Resource
    Electronic Resource
    Bioequivalence assessment of etoposide phosphate and etoposide using pharmacodynamic and traditional pharmacokinetic parameters (1996)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 24 (1996), S. 313-325 
    Details
    ISSN: 1573-8744
    Keywords: etoposide ; etoposide phosphate ; bioequivalence ; pharmacokinetics ; pharmacodynamics ; humans ; cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The bioequivalence of etoposide phosphate, a prodrug of etoposide, to etoposide was assessed in a randomized, crossover study in 29 patients with histologically established solid tumors that had failed conventional treatment. Cohorts of patients received one treatment course each of etoposide and etoposide phosphate which consisted of a 100 mg/m2 per day etoposide equivalent dose infused iv over 1 hr on a Day 1 to 5 schedule of treatment. The second course was administered 21 days later or on recovery of blood cell counts. Plasma and urine samples were collected over 24 hr on Day 1 of each course and assayed for etoposide content by a validated HPLC/UV method. Resulting data were subjected to noncompartmental pharmacokinetic analysis. Hematology profiles were obtained by collecting blood samples prior to the first course and twice a week after each course. The pharmacodynamics and pharmacokinetics of etoposide were virtually identical after the two treatments. The point estimates (90% confidence intervals) for nadir WBC, granulocytes, hemoglobin, and platelets expressed as % decrease from the baseline, and for the pharmacokinetic parameters, Cmax, and AUC0-∞, after intravenous etoposide phosphate relative to etoposide were 100% (96%, 105%), 97% (91%, 103%), 95% (82%, 109%), 95% (84%, 106%), 107% (101%, 113%), and 113% (107%, 119%), respectively. Therefore, etoposide phosphate is bioequivalent to etoposide based on pharmacokinetic and pharmacodynamic assessments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02353515
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  • 36
    Electronic Resource
    Electronic Resource
    Interspecies Pharmacokinetics of a Novel Hematoregulatory Peptide (SK&F 107647) in Rats, Dogs, and Oncologic Patients (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 794-797 
    Details
    ISSN: 1573-904X
    Keywords: allometric scaling ; peptide ; pharmacokinetics ; hematology ; infection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To study the pharmacokinetics of SK&F 107647, a novel hematoregulatory agent, in rats, dogs, and patients with non-lymphoid solid tumor malignancy. Methods. Sprague Dawley rats and beagle dogs (n = 6 each; 3 M, 3 F) were given 25 mg/kg of SK&F 107467 as an iv bolus injection, and patients (n = 6; 4 M, 2 F) received 100 ng/kg as a 2 hour iv infusion. Plasma samples were assayed for drug using either HPLC (rat and dog) or RIA (human). Results. In each species the plasma clearance (CL) of SK&F 107647 was low in relation to hepatic blood flow, and the volume of distribution (Vdss) was reflective of distribution to extracellular body water. The plasma CL in humans was near that of average glomerular filtration rate. Using allometric equations for interspecies scaling (Y = a·Wb), body-weight normalized human pharmacokinetic data were reasonably predicted using either the body weight normalized rat or the dog data. The allometric exponents (b) for CL, Vdss, and T1/2 of SK&F 107647 were 0.63, 0.94, and 0.29, respectively. Conclusions. Use of a limited pool of available animal data allowed for reasonable predictions of human pharmacokinetics of SK&F 107647.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016020221300
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  • 37
    Electronic Resource
    Electronic Resource
    Evaluation of Pharmacokinetic Studies: Is It Useful to Take into Account Concentrations Below the Limit of Quantification? (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 839-845 
    Details
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; precision ; accuracy ; limit of quantification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Based on real data, to evaluate the usefulness of taking into account samples with values below the limit of quantification (LOQ) for the evaluation of pharmacokinetic studies. Methods. To compare for two drugs, after single dose administration the pharmacokinetic parameters obtained by using a poorly sensitive assay (PSA) and a highly sensitive assay (HSA), acting as reference; To evaluate the results of pharmacokinetic studies in the light of different values for the LOQ. Results. Under certain conditions, such as homogeneous population, sufficient subject number, sufficient sampling times and acceptable accuracy (CV 〈 20%) for the concentrations, it is possible to get valuable and more reliable kinetic information by using concentrations obtained with a poor precision (CV 〉 20%). This is especially true for the parameters associated with the terminal phase, such as t1/2β and AUC, but also for parameters depending to a lesser extent on the terminal phase, such as tl/2α and AUCtn. Moreover, the mean concentration time curve is by far best defined by using all the concentrations. Conclusions. In some situations, it is preferable to use concentrations with values below the LOQ to evaluate the results of pharmacokinetic studies. However, this should not be the rule, especially when this does not bring any additional information, or when it is possible to increase the sensitivity of the bioanalytical assay.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016088609005
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  • 38
    Electronic Resource
    Electronic Resource
    Effects on the Pharmacokinetics and Pharmacodynamics in the Elderly of Coadministering Ramipril with Water, Apple Juice, and Applesauce (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 639-642 
    Details
    ISSN: 1573-904X
    Keywords: ramipril ; ACE inhibitor ; capsules ; pharmacokinetics ; pharmacodynamics ; elderly patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016022827235
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  • 39
    Electronic Resource
    Electronic Resource
    A Pharmacokinetic Approach for Evaluating Cytokine Binding Macromolecules as Antagonists (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 84-90 
    Details
    ISSN: 1573-904X
    Keywords: antibodies ; soluble receptors ; immunoadhesins, cytokines ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Cytokine binding macromolecules such as antibodies and soluble receptors sometimes produce undesirable agonist-like activities instead of the expected antagonist-like effects when the cytokine binding macromolecule extends the half-life of a short-lived cytokine. The purpose of this paper is to identify the pharmacokinetic and physicochemical properties that can cause these agonist-like activities. Methods. A simple pharmacokinetic model was used to determine whether a given cytokine binding macromolecule will function effectively as an antagonist in therapeutic situations in which cytokine is released chronically. Results. The model proposed satisfactorily fits experimental data for soluble interleukin-4 receptor and for an anti-interleukin-4 monoclonal antibody under conditions in which agonist-like and antagonist activity are observed. Conclusions. We show that the unexpected agonist-like activities result only when there is nonlinearity in the cytokine-cytokine receptor interaction and the cytokine binding macromolecule prolongs the half-life of the cytokine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016033418207
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  • 40
    Electronic Resource
    Electronic Resource
    Hemodynamic effects of intravenous elgodipine in coronary artery disease during rest and exercise, and basic pharmacokinetic parameters (1996)
    Springer
    Cardiovascular drugs and therapy 10 (1996), S. 573-580 
    Details
    ISSN: 1573-7241
    Keywords: elgodipine ; calcium channel antagonist ; coronary artery disease ; haemodynamics ; exercise ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using an echo-Doppler method (Quantascope), the hemodynamic profile of the calcium channel antagonist elgodipine (64 μg/kg, iv) was investigated in 22 patients with angina pectoris at rest and during exercise. A placebo control was used. At rest, elgodipine significantly decreased systemic vascular resistance as well as systolic and diastolic blood pressure, while increasing cardiac output and stroke volume. During supine bicycle exercise at constant workload, elgodipine significantly increased cardiac output and stroke volume, and decreased the rate-pressure-product (double product); the exercise systolic blood pressure was decreased without change in the diastolic component. Elgodipine significantly reduced the incidence and severity (self-rated pain score) of exercise-induced anginal symptoms. Heart rate was not affected by elgodipine, either at rest or during exercise. In particular, no negative inotropy could be inferred from the echo-Doppler data. In the elgodipine plasma concentration profile (HPLC), three phases of elimination with half-life times of less than 1 hour, between 3 and 7 hours, and between 10 and 24 hours may be distinguished, indicating a “shallow” and a “deep” compartment. The hemodynamic data indicate an intermediate pharmacodynamic profile of elgodipine, lying between that of other dihydropyridines and that of compounds such as verapamil or diltiazem.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00050999
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  • 41
    Electronic Resource
    Electronic Resource
    Preclinical testing of an anti-erbB-2 recombinant toxin (1996)
    Springer
    Breast cancer research and treatment 38 (1996), S. 19-25 
    Details
    ISSN: 1573-7217
    Keywords: recombinant immunotoxins ; erbB-2 ; pharmacokinetics ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The performance of OLX-209 indicates it should enter phase I clinical testing. OLX-209 is a recombinant toxin targeting theerbB-2 oncoprotein. The design of OLX-209 takes advantage of improvements in immunotoxin technology to produce a molecule that is smaller and more potent than a conventional chemically linked antibody-toxin conjugate. The targeting portion of OLX-209 is a single chain antibody structure derived from the anti-erbB-2 hybridoma, e23. This antibody has unusual specificity in that it does not bind to most normal tissue including peripheral nerve or kidney tissue. Preclinical testing showsin vitro activity against breast cancer cell lines in the pM range. Efficacy testing in five models of human cancer indicates that a dose of 43 µg/kg causes reproducible tumor regressions. Efficacy can be achieved on a variety of schedules of administration. The effective dose results in no measurable change in serum liver enzymes when delivered to mice or primates. The LD10 is over twice the effective dose in mice. The pharmacokinetics indicate a t1/2 of 50 minutes for both mice and cynomolgus monkeys. Serum concentrations of more than ten times those observed at the effective dose can be achieved in monkeys with no evidence of toxicity. Antigenicity of OLX-209 is surprisingly low. These results form the basis for the clinical testing phase for OLX-209.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01803780
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  • 42
    Electronic Resource
    Electronic Resource
    Development and Pharmacokinetics of Galactosylated Poly-L-Glutamic Acid as a Biodegradable Carrier for Liver-Specific Drug Delivery (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 880-884 
    Details
    ISSN: 1573-904X
    Keywords: drug carrier ; hepatic targeting ; poly-L-glutamic acid ; galactosylation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. A biodegradable carrier for the liver-specific delivery of drugs was developed using poly-L-glutamic acid (PLGA) modified with galactose (galactosylated PLGA or Gal-PLGA), and its feasibility was investigated in mice. Methods. 111In-PLGA and 111In-Gal-PLGAs were injected in mice and their distribution and biodegradation properties were studied. Results. After intravenous injection, 111In-PLGA was rapidly eliminated from the plasma and recovered mainly in the kidneys and urine. Approximately 15% of the dose was recovered in the liver, predominantly in the nonparenchymal cells. 111In-Gal-PLGAs were taken up by the liver parenchymal cells. Derivatives having 16 or more galactose residues were taken up by the liver to a higher extent (〉60% of the dose). The hepatic clearance of 111n-Gal-PLGAs correlated with their number of galactose residues. 111In-Gal18-PLGA was degraded into low-molecular weight products in the liver. Conclusions. The advantageous in vivo properties of Gal-PLGA as a liver-specific biodegradable carrier of drugs were demonstrated in mice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016053128569
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  • 43
    Electronic Resource
    Electronic Resource
    Bioavailability and efficacy of omeprazole given orally and by nasogastric tube (1996)
    Springer
    Digestive diseases and sciences 41 (1996), S. 475-479 
    Details
    ISSN: 1573-2568
    Keywords: omeprazole ; gastric acid secretion ; nasogastric tube ; pharmacokinetics ; pentagastrin ; cytochrome P-450 ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We compared the bioavailability and the efficacy of omeprazole provided either as encapsulated enteric-coated granules or as enteric-coated granules delivered via a nasogastric tube in 10 healthy subjects. Omeprazole reduced mean pentagastrin-stimulated peak gastric acid secretion by 85.5%±23.7% when delivered orally and by 79.6%±32.1% when delivered by nasogastric tube; the mean plasma omeprazole concentration area under the curve (AUC) was 2.02±0.79 after oral delivery and 1.74±1.89 after nasogastric tube delivery. There was no significant difference in these parameters between the two routes of administration, and there was excellent intrasubject correlation between oral and nasogastric percent acid suppression and AUC. There was a close correlation between AUC and percent acid suppression at AUC values below 0.6, and complete acid suppression at AUC values above 0.6, regardless of the delivery route. We conclude that omeprazole delivered as enteric-coated granules via nasogastric tube provides equal bioavailability and gastric acid suppression as omeprazole given orally in its proprietary formulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02282321
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  • 44
    Electronic Resource
    Electronic Resource
    Comparison of the pharmacokinetics and effects on the hemostatic system of saruplase and urokinase in patients with acute myocardial infarction (1996)
    Springer
    Journal of thrombosis and thrombolysis 3 (1996), S. 385-390 
    Details
    ISSN: 1573-742X
    Keywords: saruplase ; urokinase ; pharmacokinetics ; hemostasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the study was to compare in a single trial, using identical methodology, the pharmacokinetic properties and the effect on the hemostatic system of saruplase (unglycosylated scu-PA) and urokinase (glycosylated tcu-PA). Twenty-four patients with an acute myocardial infarction were either treated with saruplase (n = 12; 20 mg IV bolus followed by a 60 mg infusion for 60 minutes) or urokinase (n = 12; 1.5 million IU IV bolus followed by 1.5 million IU infusion for 60 minutes). Blood samples from saruplase-treated patients were analyzed for u-PA antigen and total u-PA and tcu-PA activities; those from urokinase-treated patients for u-PA antigen and tcu-PA activity. The effect of treatment on, including recovery of, plasma α2-antiplasmin, fibrinogen, and plasminogen was examined in both groups. The total clearance of urokinase (179 ± 55 ml/ min) is about half that of saruplase (406 ± 154 ml/min), and the mean residence time of urokinase (59.1 ± 22.5 minutes) is nearly twice that of saruplase (28.3 ± 7.8 minutes), which results in a slower elimination of urokinase from plasma. Whether differences in the pharmacokinetic behavior of the unglycosylated saruplase and the glycosylated urokinase observed in this study are due to the difference in glycosylation or to other factors is not resolved. The systemic effect of saruplase on α2,-antiplasmin, fibrinogen, and plasminogen is similar to that of urokinase, although retarded.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00133082
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  • 45
    Electronic Resource
    Electronic Resource
    Predicted and actual BCNU concentrations in normal rabbit brain during intraarterial and intravenous infusions (1996)
    Springer
    Journal of neuro-oncology 30 (1996), S. 7-18 
    Details
    ISSN: 1573-7373
    Keywords: BCNU ; brain cancer ; intraarterial ; pharmacokinetics ; rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Normal New Zealand White rabbits were used to compare theoretical brain concentrations (based upon pharmacokinetic modeling) with actual experimental concentrations of BCNU following intraarterial (IA) or intravenous (IV) infusions. IA infusion therapy for brain tumor patients has been promising based upon theoretical predictions but of limited effectiveness clinically. Experimentally-measured rabbit carotid artery flow rates (63.9 ± 3.4 ml/min) [mean ± 1 sem] and BCNU systemic clearances (197 ± 10.2 ml/min) predicted a theoretical IA advantage of 4.1 ± 0.2. lpsilateral brain concentrations of BCNU during and after IA infusions (20 mg/min/m2 over 15 minutes) were: 16.2 ± 2.9, 19.0 ± 3.9, 20.3 ± 2.8, 4.8 ± 2.5, 2.1 ± 1.5, and 1.7 ± 1.6 μg/gm brain at 5, 10, 15, 25, 35, and 45 minutes after infusion start. Mean concentrations at same time points in contralateral hemisphere (IA infusions) were: 7.1 ± 1.8, 9.0 ± 1.8, 10.3 ± 0.7, 4.2 ± 1.4, 2.2 ± 1.2, 2.0 ± 1.5 μg/gm brain. Concentrations in either hemisphere during IV infusions were similar to contralateral hemisphere during IA infusions. Comparison of ipsilateral: contralateral hemisphere ratios during and after IA infusions were: 3.2 ± 0.4, 2.6 ± 0.3, 2.2 ± 0.3, 1.1 ± 0.3, 1.0 ± 0.4, and 0.9 ± 0.3 at the same time points. Although these data show higher drug concentrations with IA infusions, actual values were considerably less than predicted by theoretical modeling. This discrepancy between theoretical and experimental results emphasizes need for further study of causes and remedies so that IA therapy can achieve better drug concentrations with less toxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00177438
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  • 46
    Electronic Resource
    Electronic Resource
    The disposition kinetics and residues of fenvalerate in tissues following a single dermal application to black bengal goats (1996)
    Springer
    Veterinary research communications 20 (1996), S. 265-272 
    Details
    ISSN: 1573-7446
    Keywords: fenvalerate ; goat ; pharmacokinetics ; residue ; skin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The disposition kinetics of fenvalerate were studied in goats after dermal application of 100 ml of 0.25% (w/v) solution. The insecticide persisted in the blood for 72 h. The mean (±SEM) V d(area) and apparent t 1/2 (β) were 9.92±1.44 L/kg and 17.51±2.65 h, while the AUC and ClB values were respectively 82.15±7.40 μg h/ml and 0.56±0.05 L/(kg h). Four days after the dermal application, the highest concentration of fenvalerate residues was found in the adrenal gland, followed by the biceps muscle, omental fat, liver, kidney, lung and cerebrum in that order. Fenvalerate caused hyperglycaemia but had no effect on serum protein and cholesterol levels. Serum acetylcholinesterase activities were increased after 24 h but were below the initial values from 48 to 120 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00366924
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  • 47
    Electronic Resource
    Electronic Resource
    The efficacy and pharmacokinetics of long-term low-level intraruminal administration of tricalbendazole in buffalo with induced fasciolosis (1996)
    Springer
    Veterinary research communications 20 (1996), S. 461-468 
    Details
    ISSN: 1573-7446
    Keywords: anthelmintic ; buffalo ; dosage ; efficacy ; fasciolosis ; metabolites ; pharmacokinetics ; triclabendazole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A study was conducted on the pharmacokinetics and therapeutic efficacy of triclabendazole at three low dose rates of 0.5, 1.0 and 1.5 mg/kg body weight in buffaloes experimentally infected with Fasciola gigantica. The pharmacokinetics were compared with the effects of a single intraruminal dose at 24.0 mg/kg body weight in uninfected buffaloes. At all three dose rates, an equilibrium between the absorption of triclabendazole and the disposition of its metabolites was observed by days 3 and 4 and remained almost unchanged thereafter. Continuous daily dosing at 1.5 mg/kg body weight proved to be efficacious against liver fluke infection in buffaloes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00419183
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  • 48
    Electronic Resource
    Electronic Resource
    Preliminary pharmacokinetic and pharmacodynamic studies on flunixin meglumine in donkeys (1996)
    Springer
    Veterinary research communications 20 (1996), S. 469-472 
    Details
    ISSN: 1573-7446
    Keywords: donkey, flunixin ; pharmacokinetics ; prostaglandin ; thromboxane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00419184
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  • 49
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    Electronic Resource
    The effect of induced fever on the biokinetics of norfloxacin and its interaction with probenecid in goats (1996)
    Springer
    Veterinary research communications 20 (1996), S. 473-479 
    Details
    ISSN: 1573-7446
    Keywords: fever ; fluoroquinolone ; goat ; norfloxacin ; pharmacokinetics ; probenecid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The kinetic profiles of norfloxacin were evaluated in afebrile, febrile and probenecid pre-treated (70 mg/kg orally) febrile goats after a single intravenous (i.v) dose (5 mg/kg). Fever was induced and maintained for 12 h by injecting Escherichia coli endotoxin (0.2 μg/kg, i.v.) and repeating it in half the dose (0.1 μg/kg) 5 h later. The plasma pharmacokinetic values for norfloxacin were best represented using a two-compartment open model. The peak norfloxacin plasma level of 90.52±3.18 μg/ml attained in the probenecid pre-treated febrile goats was higher than that in the febrile (75.46±0.72 μg/ml) or afebrile goats (62.25±1.23 μg/ml). ClB and K el values were significantly (p〈0.01) decreased in febrile compared with afebrile goats. These values were further reduced in febrile goats after probenecid pre-treatment. However, t 1/2β was not affected by the fever-probenecid interaction. Norfloxacin may be used as an infusion with probenecid in caprine diseases where very high plasma levels are required to combat resistant organisms such as Bacteroides.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00419185
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    Synthesis and structural characterization of enantiopure levodropropizine (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 6-10 
    Details
    ISSN: 0899-0042
    Keywords: enantiopure levodropropizine ; synthesis ; (R)-glycidol ; enantiomeric separation ; chiral HPLC ; enantiomeric enrichment ; binary melting point phase diagram ; crystal structure determination ; intermolecular hydrogen-bonding interactions ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Enantiopure levodropropizine can be synthesized in high yield by the direct nucleophilic addition of 1-phenylpiperazine to (R)-glycidol followed by recrystallization in absolute ethanol. A chiral HPLC method has been developed for the determination of its optical purity. The enantiomeric enrichment behavior of this compound in the recrystallization process is discussed according to its binary melting point phase diagram. Single crystal x-ray structural analysis shows the intermolecular hydrogen-bonding interactions between the hydroxyl and piperazinyl groups within the crystal lattice of levodropropizine. © 1996 Wiley-Liss, Inc.
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    In vitro study of the metabolic effects of D-amino acids (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 24-29 
    Details
    ISSN: 0899-0042
    Keywords: CHO cells ; HeLa cells ; lipid peroxidation ; catalase ; D-amino acids ; L-amino acids ; toxicity ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: While the L-configuration of amino acids predominates in all known living systems, D-enantiomers of amino acids have been detected with highly sensitive chromatographic techniques in human physiological fluids. In the present study, the survival of Chinese hamster ovary cells (CHO) and HeLa cells was inhibited by exposure to high concentrations of some D- or L-amino acids. Inhibition of colony formation, though, was not necessarily observed to be chiral-dependent. Some L-amino acids (LAAS) were found to be toxic while other D-amino acids (DAAS) were innocuous in both cultures. This is contradictory to the previous observations that DAAS were generally considered to be harmful. Frequently it was implied, although not experimentally proven, that the LAAS were not toxic. One of the metabolites produced by oxidative deamination of D- or LAAS is hydrogen peroxide (H2O2), a reactive oxygen species (ROS) that is decomposed by catalase. Increased intracellular H2O2 can result in peroxidation of lipids. We measured catalase activity and the lipid peroxide levels (LPO) after incubating cells in either D- or LAAS. The amino acids (AAS) that were found to inhibit colony formation were found to be associated with higher levels of catalase activity and LPO. Therefore, we hypothesize that enhanced ROS generation may be, in part, responsible for the observed toxicity of some amino acids. © 1996 Wiley-Liss, Inc.
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    Ion channels as pharmacologic receptors: The chirality of drug interactions (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 35-38 
    Details
    ISSN: 0899-0042
    Keywords: ion channels ; receptors ; state-dependent interactions ; stereoselectivity ; local anesthetics ; 1,4-dihydropyridines ; Ca2+ channels ; Na+ channels ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Ion channels are pharmocologic receptors and as such exhibit stereoselective interactions with drugs. Ion channels are conformationally mobile transmembrane proteins existing in a number of open and closed states. Drug interactions with these different states may differ quantitatively and qualitatively. Stereoselectivity may not be a constant factor and may change according to channel state as determined by stimulus mode or experimental conditions. Selected examples are cited for Na+ and Ca2+ channels. © 1996 Wiley-Liss, Inc.
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    Enantiomeric composition and prevalence of some bicyclic monoterpenoids in amber (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 39-48 
    Details
    ISSN: 0899-0042
    Keywords: α-pinene ; β-pinene ; camphene ; limonene ; borneol ; isoborneol ; succinite ; geochemistry ; stereochemistry ; pine resins ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Among the more prevalent chiral monoterpenoid compounds in conifers are α-pinene, β-pinene, and smaller amounts of camphene and limonene. The most prevalent chiral monoterpenoid compounds in fossilized resin (referred to as amber in this paper) appear to be borneol, isoborneol, and camphene. Most of these compounds have easily measured enantiomeric excesses. The borneol and isoborneol in some amber samples have pronounced enantiomeric excesses despite the fact that they are tens of millions of years old. The enantiomeric ratios of the monoterpenoids in different ambers vary tremendously and often are distinct. However, in any single amber sample, the stereochemistry (absolute configuration) of the excess monoterpenoid enantiomers appears to be identical. The camphene in amber may be a secondary reaction product formed over time, possibly from the dehydration of borneol. Although a compound's original stereochemistry can be preserved, it also may diminish with the number and type of chemical transformations over geological time. The monoterpene enantiomeric ratios in modern conifer resins vary tremendously. Future stereochemical studies are outlined that could provide the data necessary for more exact geochemical interpretations and possibly for obtaining pertinent paleobiological information. © 1996 Wiley-Liss, Inc.
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    Separation of enantiomers using vancomycin in a countercurrent process by suppression of electroosmosis (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 77-83 
    Details
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Excellent separations were achieved using a coated column to suppress electroosmotic flow and employing a countercurrent process between chiral selector and racemic solute. Using the macrocyclic antibiotic vancomycin as a chiral selector in capillary electrophoresis the resolution of nonsteroidal antiinflammatories and dansyl amino acids was achieved. Improvement in sensitivity due to the elimination of background absorbance and increased efficiency due to the removal of wall adsorption effects are both achieved using this technique. © 1996 Wiley-Liss. Inc.
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    Role of capillary electrophoresis methods in the drug development process (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 108-121 
    Details
    ISSN: 0899-0042
    Keywords: chiral purity ; pharmaceutical ; achiral ; cyclodextrin ; SBE cyclodextrin ; purity ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In the past several years, capillary electrophoresis (CE) has generated considerable interest from pharmaceutical companies for control of both the chiral and achiral purity of bulk drugs and drug products. This paper evaluates the use of CE as: (1) a technique complementary to HPLC for the determination of peak homogeneity of a drug, (2) for determination of chiral purity, and (3) for determination of achiral purity. It would be greatly advantageous if CE could be used to determine both the chiral and achiral purity in a single assay. This investigation compares the results obtained for the separation of the enantiomers of duloxetine using several neutral cyclodextrins to those obtained using anionic cyclodextrins (sulfobutyl ether derivatives) as chiral selectors added to the separation buffer. In addition, it reports chiral separations obtained by using neutral cyclodextrins in a sulfonic acid-coated capillary column, which give a negatively charged capillary surface and electro-osmotic flow even in low pH buffers. The possible mechanism of separation is discussed. © 1996 Wiley-Liss, Inc.
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    Use of subcritical fluid chromatography for the separation of enantiomers using packed cellulose based stationary phase (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 157-162 
    Details
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Investigations into the parameters affecting the enantiomeric separation of an intermediate in the synthesis of a drug targeted for cardiac arrhythmia is presented. The separation was achieved under subcritical fluid chromatography using CO2 modified with methanol and co-modifiers isopropyl amine and methylene chloride. The stationary phase was a cellulose based stationary phase manufactured under the trade name Chiracel OB. The results showed the addition of methylene chloride had a noticeable effect on resolution while the separation factor, α, remained constant. The co-modifier, isopropyl amine, did not considerably influence the resolution, or separation factor. Temperature studies were performed in order to establish the thermodynamic parameters of the interaction between the enantiomers and the stationary phase. Plots of In k′ vs. 1/T proved to be curved, while plots of In α vs. 1/T were linear. © 1996 Wiley-Liss, Inc.
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    Copper(II) complexes of N2-alkyl-(S)-amino acid amides as chiral selectors for dynamically coated chiral stationary phases in RP-HPLC (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 189-196 
    Details
    ISSN: 0899-0042
    Keywords: chiral ligand exchange chromatography ; chiral coating ; chiral discrimination ; chiral copper(II) complexes ; amino acids ; amino acid esters ; amino acid amides ; hydroxy acids ; dipeptides ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Copper(II) complexes of N2-octyl-(S)-phenylalaninamide (Noc-Phe-NH2), N2-dodecyl-(S)-phenylalaninamide (Ndo-Phe-NH2), and N2-octyl-(S)-norleucinamide (Noc-NLeu-NH2), dynamically adsorbed on a reversed-phase C18 column, were able to perform the direct enantiomeric separation of unmodified amino acids, amino acid amides and esters, hydroxy acids, and dipeptides by elution with aqueous or mixed aqueous-organic solutions containing copper(II) sulphate or acetate. The role played by several parameters in the separation procedure was examined with the copper(II) complex of Noc-Phe-NH2 [concentration of the copper(II) ion in the eluent, pH and eluent polarity, amount of adsorbed selector]. The separation was shown to occur entirely on the stationary phase. The mechanism of chiral discrimination is discussed in terms of the chromatographic parameters and of the structure of the copper(II) complexes in solution and in the solid state. The chiral stationary phase maintained its separation ability for about 3 months. However, the column could be easily restored by recovering the selector with methanol and repeating the loading procedure. © 1996 Wiley-Liss, Inc.
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    Masthead (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996) 
    Details
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/chir.530080201
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    Enantiomeric enrichment of non-racemic mixtures of binaphthol with non-chiral packings (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 234-243 
    Details
    ISSN: 0899-0042
    Keywords: enantiomeric ; non-racemic mixtures ; binaphtol ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: It is shown that chromatography with achiral phases of non-racemic mixture of binaphthol can furnish fractions which differ in enantiomeric excess. The first fraction contains one pure enantiomer i.e., has an enantiomeric excess (ee %) close to 100% and the following fractions have an ee % close to 0% (racemic mixture). As a consequence, such chromatography may be used to enrich a non-racemic mixture of binaphthol in one enantiomer. In this paper a model is proposed allowing us to calculate with good accuracy the experimental elution curves. This simple model is capable of using only a few chromatographic experiments to predict the enantiomeric enrichment of a non-racemic mixture and to calculate precisely the retention time of each fraction. © 1996 Wiley-Liss, Inc.
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    Relationship between resolution and analysis time in chiral subcritical fluid chromatography (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 249-257 
    Details
    ISSN: 0899-0042
    Keywords: chiral SubFC resolution ; analysis time ; column efficiency ; library of chiral columns ; selectivity ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A model is presented that predicts a defined relationship between chiral SubFC resolution and analysis time. This model is based upon ideal chromatographic behavior and requires column efficiency and selectivity to be independent of mobile phase modifier level and flow rate. The validity of these assumptions was found to be imperfect but acceptable for two model compounds on two commonly used chiral columns.A major implication of the model is that the maximum resolution obtainable with a particular column and mobile phase modifier may be predicted from one injection. The retention time required to obtain a desired resolution is also calculable. This information enables the practitioner to discern quickly the futility of method development efforts. Insufficient maximum resolution predicted from the first injection would require an increase in selectivity to achieve a useful separation. Selectivity may then be altered by temperature, modifier, or stationary phase. The increased column efficiency of SubFC at typical flow rates rescues separations that fail by HPLC, thus shrinking the practitioner's required library of chiral columns. This work demonstrates that SubFC also allows the practitioner to skim through that library very quickly. © 1996 Wiley-Liss, Inc.
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    Separation of R- and S-Thalidomide by Reversed-Phase HPLC with β-cyclodextrin in the mobile phase (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 11-17 
    Details
    ISSN: 0899-0042
    Keywords: thalidomide enantiomers ; mobile phase additive ; stereoselective analysis ; high-performance liquid chromatography ; chiral separation ; β-cyclodextrin ; inclusion complex ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: R- and S-Thalidomide were resolved by reversed-phase HPLC on a C-18 column with β-cyclodextrin in the mobile phase. As the concentration of β-cyclodextrin was increased stepwise from 0 to 20 mM, enantiomeric resolution increased and retention times decreased significantly. The influence of different organic modifiers in the mobile phase were evaluated, and ethanol, among others, proved to be effective. Equilibrium constants for the formation of β-cyclodextrin inclusion complexes of R- and S-thalidomide in EtOH-buffer (5:95) were calculated to be 64 and 76 M-1, respectively. © 1996 Wiley-Liss, Inc.
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    Masthead (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996) 
    Details
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/chir.530080101
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    Application of force field calculations to the prediction of chirally discriminating chromatographic behaviour for β-CDs (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 58-66 
    Details
    ISSN: 0899-0042
    Keywords: molecular mechanics ; HPLC ; chiral separation ; methylphenobarbitone ; hexobarbitone ; ibuprofen ; mandelic acid ; ephedrine ; pseudoephedrine ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: β-Cyclodextrin and its derivatives have been utilised to effect chiral separation in HPLC and CZE, both as stationary phases and mobile phase additives. The basis of the method is assumed to depend upon the formation of inclusion complexes of differing stabilities between enantiomeric analytes and the cyclodextrin, resulting in a differential dynamic distribution between chromatographic phases. In this study, force field calculations have been employed to model the inclusion complexes of enantiomeric brompheniramine, ephedrine, pseudoephedrine, ibuprofen, mandelic acid, methylphenobarbitone, and hexobarbitone with β-cyclodextrin. The resulting values for Δ(ΔH), the difference in enthalpy of complex formation between enantiomeric pairs has been compared with literature chromatographic data to explain the ability of the systems to achieve enantiomeric separations. © 1996 Wiley-Liss, Inc.
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    Optical resolution by preferential crystallization of (RS)-2-amino-3-chloropropanoic acid hydrochloride (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 197-200 
    Details
    ISSN: 0899-0042
    Keywords: optical resolution ; conglomerate ; preferential crystallization ; optically active 2-amino-3-chloropropanoic acid ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The racemic structures of (RS)-2-amino-3-chloropropanoic acid [(RS)-ACP] and (RS)-2-amino-3-chloropropanoic acid hydrochloride [(RS-ACP·HCl] were examined to obtain (R)- and (S)-ACP via optical resolution by preferential crystallization. The melting point, infrared spectrum, solubility, and ternary solubility diagram suggested that (RS)-ACP·HCl exists as a conglomerate and that (RS)-ACP forms a racemic compound. Optical resolution by preferential crystallization of (RS)-ACP·HCl was successfully achieved to yield (R)- and (S)-ACP·HCl. Optically pure (R)- and (S)-ACP were obtained from the purified (R)-and (S)-ACP·HCl, respectively. © 1996 Wiley-Liss, Inc.
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    Disposition of CS-670, a novel nonsteroidal anti-inflammatory drug, and its metabolites in healthy human volunteers (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 207-213 
    Details
    ISSN: 0899-0042
    Keywords: CS-670 ; anti-inflammatory drug ; stereoselective metabolism GC-MS ; diastereomer HPLC ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: CS-670, a novel nonsteroidal anti-inflammatory drug, is a racemic prodrug. Plasma concentrations and urinary excretion of CS-670 and its metabolites were determined in experimental subjects after oral administration at a single 120 mg dose. CS-670 and four metabolites, the saturated ketone (M-A), unsaturated-alcohol (M-B), cis-alcohol (M-C), and trans-alcohol (M-D), were quantitated by GC-MS. The major metabolites in human plasma were M-B, M-C, and M-D and their terminal half-lives (t½) were 0.9, 2.6, and 1.2 h, respectively. The total recovery in the urine was 26% of the dose, but unchanged CS-670 accounted for less than 2% over a 48 h period. In addition, the absolute configurations of the metabolites were examined by HPLC after derivatization with chiral reagents. It was found that the configuration of the propionic acid moiety of the metabolites, M-B, M-C, and M-D, in human plasma, was rapidly inverted from (-)-(R) to the (+)-(S) configuration in stereoselective biotransformation. Furthermore, the configurations of the 1′- and 2′-carbons of M-C and M-D, were found to be (1′R,2′S) and (1′R,2′S), respectively. These results show that CS-670 is readily biotransformed by chiral inversion of the 2-arylpropionic acid moiety and stereoselective reduction of the α, β-unsaturated ketone moiety in humans. © 1996 Wiley-Liss, Inc.
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    Nominations for the 1997 Benedetti-Pichler award (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 356-356 
    Details
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/chir.530080406
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    Convenient lipase-assisted preparation of both enantiomers of suprofen, a non-steroidal anti-inflammatory drug (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 377-380 
    Details
    ISSN: 0899-0042
    Keywords: NSAIDs ; esterification ; resolution ; Candida antarctica lipase ; Mucor miehei lipase ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The resolution of rac-suprofen (1) catalysed by lipase in organic solvents was investigated. Direct esterification of rac-1 with methanol in dichorometane catalysed by Novozym® 435 furnished the pharmacologically active (+)-(S)-suprofen as unreacted product with excellent enantiomeric excess. The same procedure in toluene using Mucor miehei lipase adsorbed in Celite as catalyst afforded (-)-(R)-suprofen with good optical purity. © 1996 Wiley-Liss, Inc.
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    Dichloro-, dimethyl-, and chloromethylphenylcarbamate derivatives of cyclodextrins as chiral stationary phases for high-performance liquid chromatography (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 402-407 
    Details
    ISSN: 0899-0042
    Keywords: enantioseparation ; HPLC ; cyclodextrin ; phenylcarbamate ; chiral stationary phase ; optical resolution ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: New dichloro-, dimethyl-, and chloromethylphenylcarbamate derivatives of cyclodextrins (CDs) were prepared and their enantiomeric recognition abilities were evaluated as chiral stationary phases (CSPs) in normal phase high-performance liquid chromatography (HPLC). The effects of the type of cyclodextrins, the nature and position of the substituents on the phenyl ring, binding mode and spacer on the chiral recognition were studied in detail. No marked change of chiral recognition abilities was established by reversing the binding side of CDs (i.e., by the narrower [primary] opening of the cone-shaped CD to silica gel with the wider [secondary] opening sides). This result indirectly proves the previously drawn conclusion about the minor role of inclusion phenomena in chiral recognition in this case. Nevertheless, chiral recognition of these CSPs toward some compounds critically depends on the type of CDs used. All CD derivatives described in this study show rather low enantiomeric resolving abilities compared with corresponding polysaccharide (cellulose and amylose) derivatives, although very high enantioselectivity of separation was observed for a few compounds, such as racemic flavanone and cyclopropanedicarboxilic acid dianilide. © 1996 Wiley-Liss, Inc.
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    Toxic doses of rac-, (-)-(S)- and (+)-(R)-propranolol in rats and rabbits (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 411-417 
    Details
    ISSN: 0899-0042
    Keywords: rac-propranolol ; enantiomers ; drug intoxication ; cardiovascular function ; respiratory function ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The contribution of the individual enantiomers ([+]-[R]- and [-]-[S]-propranolol) to rac-propranolol intoxication was studied in anaesthetized, spontaneously breathing (SB) rats and artificially ventilated (AV) rats and rabbits. In the SB rat, propranolol (30 mg.kg-1.h-1 i.v.) decreased heart rate and mean arterial blood pressure and caused hypoventilation, serious hypoxaemia, respiratory acidosis, and death by respiratory arrest. Survival time (ST) in the (+)-(R)-propranolol group (ST 91 ± 5 min) was significantly longer than in the rac-propranolol group (ST 68 ± 6 min). In AV rats and rabbits toxic doses of rac-, (-)-(S)- and (+)-(R)-propranolol, 30 mg.kg-1.h-1 and 15 mg.kg-1.h-1 i.v., respectively, induced comparable effects on haemodynamic variables as in the SB rat. Artificial ventilation lengthened ST by a factor of three to four in rats. In the AV rat, ST's were not significantly different between the rac-, (-)-(S)- and (+)-(R)-propranolol groups. In the rabbit, as in the SB rat, ST in the (+)-(R)-propranolol group was significantly longer than ST's in the rac- and (-)-(S)-propranolol groups. The acute respiratory acidosis in SB rats and the prolonged ST in AV rats suggest that respiratory failure is the primary and cardiovascular failure the secondary cause of death in propranolol intoxication. The potentiation of the toxic effect of the enantiomers observed after dosing the racemate instead of the pure enantiomers could not be explained by a stereoselective difference in plasma propanolol concentration. © 1996 Wiley-Liss, Inc.
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    Masthead (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996) 
    Details
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/chir.530080601
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    Chiral discrimination by ligand-exchange chromatography: A comparison between phenylalaninamide-based stationary and mobile phasesThis work is dedicated to the memory of Professor Emanuel Gil-Av. (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 452-461 
    Details
    ISSN: 0899-0042
    Keywords: enantiomers ; HPLC ; DNS-animo acids ; fluorescence quenching ; ligand-exchange mechanism ; adsorption ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The copper(II) complexes of two new diastereomeric ligands, N2-(R)- and N2-(S)-2′-hydroxypropyl-(S)-phenylalaninamide [(R, S)-1 and (S, S)-1], have been used as additives to the eluent in high-performance liquid chromatography (HPLC) reversed phase for the chiral separation of DNS-amino acids. The aim was that of comparing the separation process obtained by the chiral eluent with that obtained by an analogous bonded stationary phase containing (S)-phenylalaninamide, previously studied [CSP-(S)-Phe-NH2]. The affinity of the ternary complexes for the C18 column was determined by adsorption experiments in HPLC. It was shown that the two systems (chiral eluent, chiral stationary phase) work according to different mechanisms. Ternary complex formation in solution was studied by fluorescence spectroscopy. It was shown that chiral separation with the Cu(II) complexes added to the eluent was determined by the relative affinities of the ternary complexes for the column-stationary phase rather than by their stabilities in solution. With CSP-(S)-Phe-NH2 the separation is accounted for by the relative stabilities of the ternary complexes, which depends mainly on the “allowed” geometry of the complex and on the steric repulsion of the amino acid side chain with the spacer. © 1996 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
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    Method development in liquid chromatography with a charged cyclodextrin additive for chiral resolution of rac-amlodipine utilising a central composite design (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 466-476 
    Details
    ISSN: 0899-0042
    Keywords: rac-amlodipine ; amlodipine ; liquid chromatography ; chiral ; charged cyclodextrin ; optimisation ; central composite design ; mobile phase additive ; experimental design ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A negatively charged derivative of β-cyclodextrin, sulphobutyl ether-β-cyclodextrin (SBE-β-CD), was examined as a chiral mobile phase additive in reversed-phase high-performance liquid chromatography for the enantiomeric resolution of the calcium channel blocker rac-amlodipine. Theoretical and practical aspects are discussed for setting up a central composite design applicable to any analytical method. These include the correct location of factor points for maintaining orthogonality within the design and the augmentation of centrepoint experiments to allow a larger factor space by increasing the distance of axial star points. Optimised separation was achieved using a reverse-phase column with eluent comprising: acetonitrile (ACN) - potassium dihydrogen phosphate (pH 3.93) containing 2.66 mM SBE-bgr;-CD (26.5:73.5% v/v) at a flow rate of 1.0 ml/min. This yielded a Kaiser peak separation index, Pi = 0.96, at tR2 = 52 min with satisfactory reproducibility, relative standard deviation values: tR1, 0.39%; tR2, 0.47% (n = 5). These experimental results were in excellent agreement with those predicted by the SAS software package for a chromatographic response function model. Multiple regression analysis in four dimensions, with three response models based on Rs, Pi, and a function of Pi, produced response surfaces which revealed zones of optimum robustness and illustrated the interactions involved between the key chromatographic factors. Putative proposals for a mechanism involving the interaction of each of the positively charged enantiomers with the negatively charged cyclodextrin are also discussed. These examine the possibility of ion-pairing and inclusion phenomena to account for the excellent resolution observed. © 1996 Wiley-Liss, Inc.
    Additional Material: 11 Ill.
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  • 73
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    Lambda-carrageenan: A novel chiral selector for capillary electrophoresis (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 503-510 
    Details
    ISSN: 0899-0042
    Keywords: enantioseparations ; carrageenans ; sulfated polysaccharides ; beta blockers ; tryptophan and derivatives ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Lambda-carrageenan, a linear high molecular weight sulfated polysaccharide, has been employed as a chiral selector in capillary electrophoresis for the separation of enantiomers of weakly basic pharmaceutical compounds. The racemic compounds that were enantioresolved included propranolol, pindolol, tryptophanol, laudanosine and laudanosoline. In addition, the diastereomeric pair of cinchonine and cinchonidine were also resolved. Method conditions such as buffer pH, electrolyte concentration, column temperature, and chiral selector concentration were found to be important for improvement of enantioselectivity. © 1996 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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  • 74
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    Chiral aminophosphonate eluent for enantiomeric analysis of amino acids (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 122-125 
    Details
    ISSN: 0899-0042
    Keywords: aminophosphonic acids ; asymmetric synthesis ; chiral HPLC ; ligand-exchange chromatography ; enantiomeric analysis ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: An aqueous solution of the (+)-monoethyl ester of N-(l′-hydroxymethyl-)propyl-α-aminobenzylphosphonic acid has been proposed as a suitable chiral eluent for enantiomeric analysis of amino acids by ligand-exchange chromatography. Asymmetric synthesis of the chiral selector using (-)-(R)-2-aminobutan-1-ol as a starting reactant is described. The dependence of the parameters of separation of valine enantiomers on concentration of the complexing ion, pH, and temperature has been investigated. It is shown that the order in which enantiomers are eluted from a column depends on the concentration of the complexing ion and pH. © 1996 Wiley-Liss, Inc.
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    Carbohydrate carbamate coated onto microporous silica: Application to chiral analysis of commercial pharmaceutical drugs (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 143-146 
    Details
    ISSN: 0899-0042
    Keywords: Cellulose tris-(3,5-dimethylphenyl carbamate) ; resolution ; tetramisole ; propanolol ; microporous APS-silica ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enantioselectivity of a series of chiral analytes was examined on tris-(3,5-dimethylphenyl carbamate) coated onto microporous APS-silica. The effects of the nature of the carbohydrate, the weight ratio of carbamate/support and the type of alcohol present in the mobile phase were investigated. Among the chiral analytes examined, propanolol showed an extremely good resolution. The resolution of tetramisole was optimized and the method developed was shown to be suitable for analysis of the drug in commercial tablets and in a suspension. © 1996 Wiley-Liss, Inc.
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    Erratum: Froimowitz, M., Cody, V. Absolute configurations and conformations of the opioid agonist and antagonist enantiomers of picenadol. Chirality 7:518-525, 1995. (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 352-352 
    Details
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: No abstract.
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    13C nuclear spin-spin relaxation times (T2Cs) of enantiomers in the presence of column packing material and solvents for chiral discrimination HPLC (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 372-376 
    Details
    ISSN: 0899-0042
    Keywords: 13C NMR ; chiral recognition difference ; elution order ; cellulose tris(4-methylbenzoate) ; 1-phenylethanol ; 1-indanol ; 1,2,3,4-tetrahydro-1-naphthol ; glutethimide ; Tröger's base ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: To elucidate chiral recognition difference between pairs of enantiomers which interacted with a cellulosic stationary phase of chiral discrimination high performance liquid chromatography (HPLC), 13C NMR spectroscopy was applied for enantiomers of 1-phenylethanol, 1-indanol, 1,2,3,4,-tetrahydro-1-naphthol, glutethimide, and Tröger's base. Their 13C nuclear spin-spin relaxation times (T2Cs) and spectra were obtained in deuterated HPLC solvents in the presence of column packing material made of cellulose tris(4-methylbenzoate) coated on silica gel. The first-eluted enantiomers on the HPLC showed longer T2Cs and stronger signal intensities of 13C NMR spectra than the second-eluted enantiomers. These results indicated that the chiral recognition difference of enantiomers was observed by their T2Cs and intensities of 13C NMR spectra. The T2C difference was found to reflect the retention order of enantiomers on the chiral HPLC column. © 1996 Wiley-Liss, Inc.
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    Sixth International Symposium on chiral discrimination (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 1-1 
    Details
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: No abstract.
    Type of Medium: Electronic Resource
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    New synthesis of (+)-(S)-halothane (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 3-5 
    Details
    ISSN: 0899-0042
    Keywords: stereospecific decarboxylation ; asymmetric synthesis ; inhalational anesthetic ; halothane ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A new synthesis of non-racemic halothane (1-bromo-1-chloro-2,2,2-trifluoroethane) is reported. The stereospecificity of the key reaction, decarboxylation of a salt of optically enriched 1-bromo-1-chloro-2,2,2-trifluoropropionic acid to give halothane, is shown to be highly dependent on the nature of the cation. When the cation is trialkylammonium, a high level of stereospecificity is observed. © 1996 Wiley-Liss, Inc.
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    Pharmacokinetics of ibutilide and its enantiomers in dogs (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 18-23 
    Details
    ISSN: 0899-0042
    Keywords: racemate ; enantiomer ; bioavailability ; pharmacokinetic ; ibutilide ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Ibutilide fumarate, a new drug for the treatment of cardiac arrhythmias, contains a stereogenic center bearing a secondary alcohol group. Several single dose and multiple dose studies of racemic ibutilide or its enantiomers were performed by the oral and intravenous routes in dogs. A chiral assay was used to examine racemization and the individual enantiomer pharmacokinetics. Following low oral or intravenous doses (approximately 0.3 mg/kg), the pharmacokinetics of the enantiomers were nearly identical, with no substantial chiral conversion. Both enantiomers exhibited high clearance rates, large volumes of distribution, and low oral bioavailability. As the dose increased, pharmacokinetic differences between the enantiomers were observed. The greatest differences (3-fold) were seen after oral administration at 4 mg/kg, indicating that first-pass metabolism of ibutilide was highly enantioselective at high doses. The clearances of the enantiomers differed by up to 34% at 5 mg/kg followed intravenous administration of the racemate. At high doses, other non-linear pharmacokinetic behavior was also apparent. The intravenous clearance of ibutilide declined from 5.3 L/h/kg at 0.3 mg/kg to 3.7 L/h/kg at a dose of 5 mg/kg. The absolute oral bioavailability of the racemate increased from 2% at 0.3 mg/kg to as much as 84% at 5 mg/kg. © 1996 Wiley-Liss, Inc.
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    Determination of the enantiomeric composition of mexiletine and its four hydroxylated metabolites in urine by enantioselective capillary gas chromatography (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 30-34 
    Details
    ISSN: 0899-0042
    Keywords: gas chromatography ; modified β-cyclodextrin column ; chiral separation ; assay ; mexiletine ; hydroxylated metabolites ; urine ; conjugation/deconjugation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enantiomers of mexiletine and four of its hydroxylated metabolites were directly separated by capillary gas chromatography using a heptakis(6-O-tert-butyl-dimethylsilyl-2,3-di-O-methyl)-β-cyclodextrin column. The method was applied to the analysis of urine samples from cancer patients who were treated with racemic mexiletine as part of a study of the use of mexiletine in the relief of neuropathic pain. Samples analyzed before and after deconjugation of the urine with β-glucuronidase/arylsulfatase showed a high stereoselectivity in the formation and conjugation of these compounds. © 1996 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
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    Evaluation of the concentration and enantiomeric purity of selected free amino acids in fermented malt beverages (beers) (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 49-57 
    Details
    ISSN: 0899-0042
    Keywords: racemization ; fermented beverages ; beer ; D-amino acids ; D-leucine ; D-phenylalanine ; D-proline ; cyclodextrin columns ; column switching ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Even though amino acids are important trace components in the brewing of beers, they have not been extensively evaluated in these beverages. Studies involving the enantiomeric composition of these amino acids are even less prevalent. A brief summary of the brewing process for malt beverages is given. The total concentration and enantiomeric composition of three amino acids (leucine, phenylalanine, and proline) were determined in 25 different beers. Proline tended to have the highest average absolute concentration and the lowest percentage of the D-enantiomer in most samples. In some cases the relative amounts of D-phenylalanine and D-leucine exceeded 10% of the individual amino acids. The enantiomeric composition of the amino acids in different beer samples did not vary as extensively as the absolute concentrations. The reason for the concentration differences between proline and the other amino acids is discussed. A knowledge of amino acid concentrations and enantiomeric compositions appears to be useful in characterizing specific beers and brewing processes. © 1996 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
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    Use of mathematically enhanced spectral analysis and spectral contrast techniques for the liquid chromatographic and capillary electrophoretic detection and identification of pharmaceutical compounds (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 67-76 
    Details
    ISSN: 0899-0042
    Keywords: spectral analysis ; spectral contrast ; HPLC ; MECC ; peak homogeneity ; peak tracking ; method development ; photodiode array detection ; isomers ; enantiomers ; diastereomers ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The use of mathematically enhanced ultraviolet/visible (UV/VIS) absorbance spectral analysis and spectral contrast software techniques in high performance liquid chromatography (HPLC) and micellar electrokinetic capillary electrophoresis (MECC) as an aid for the determination of peak homogeneity, identification, and tracking during method development was investigated. Various structurally similar pharmaceutical compounds, and compounds present as either cis/trans isomers, diastereomers, or enantiomers were used as test compounds to probe the limits of this technique. Two tricyclic antidepressants, nortriptyline and imipramine, were employed to study the effects of HPLC mobile phase composition and pH on the ability to identify and track peaks during method development. It was found that method changes altered the spectral matches used for identification, but not enough to cause incorrect peak identification. It was also shown using HPLC that the cis/trans isomers of doxepin and the diastereomers ephedrine and pseudoephedrine could be distinguished.The mathematically enhanced spectral analysis and spectral contrast software techniques were also employed with MECC. Peaks tracking during method development as pH and the concentration of surfactant changes is shown for a separation of various penicillin type antibiotics. It was shown that during chiral MECC (CMECC) analyses ephedrine/pseudoephedrine diastereomers as well as ephedrine enantiomers could be distinguished. The determination of enantiomers is possible in CMECC since enantiomers are eluted as diastereomeric complexes, as opposed to HPLC where they are eluted in their native state. © 1996 Wiley-Liss, Inc.
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    Polar organic chiral separation of propranolol and analogues using a β-cyclodextrin bonded stationary phase (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 126-130 
    Details
    ISSN: 0899-0042
    Keywords: cyclodextrin ; chiral ; propranolol ; chromatography ; stationary phase ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A β-cyclodextrin bonded stationary phase was employed for the enantioresolution of propranolol and several analogues in conjunction with various polar organic mobile phases. The effects of structural alterations in the non-polar regions of the analytes were found to exert profound changes upon chiral resolution and capacity values, indicating that features which cannot hydrogen-bond with the cyclodextrin molecule still play an important role in this chiral recognition process. This was linked to a repulsive steric effect facilitating the necessary conditions for chiral resolution. The degree of ionization of the analytes and the type and concentration of organic modifier used were also seen to influence the analytes1 enantio-selectivity and capacity values. © 1996 Wiley-Liss, Inc.
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    Enantiomeric resolution of chiral sulfoxides on polysaccharide phases by HPLC (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 147-152 
    Details
    ISSN: 0899-0042
    Keywords: amylose ; (S)-α-methylbenzyl carbamate ; chiral sulfoxides ; microporous silica ; polysaccharide phases ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enantiomeric resolution of chiral sulfoxides was investigated on amylose (S)-α-methylbenzyl carbamate phase coated on aminopropylated 7 μm silica with 500Å diameter pores. This was shown to be very successful in the separation of alkyl/aryl, aryl/aryl, and non-aromatic sulfoxides. The effect of pore size using naked silica was also investigated, demonstrating that the pore size does not affect the resolution. © 1996 Wiley-Liss, Inc.
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    Direct enantioselective separation of some propranolol analogs by HPLC on normal and reversed cellulose chiral stationary phases (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 153-156 
    Details
    ISSN: 0899-0042
    Keywords: propranolol enantiomers ; fluorinated analogs ; chiralcel OD and chiralcel OD-R columns ; chiral recognition mechanism(s) ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enantiomeric separation of several racemic aryloxyaminopropan-2-ol derivatives related to propranolol on normal and reversed phase of cellulose tris (3,5-dimethylphenylcarbamate) chiral stationary phases known as Chiralcel OD and Chiralcel OD-R were studied. It was observed that the chiral separation depends on the substitution pattern of the aryl group, i.e., 1-naphthyl, 2-naphthyl, and phenyl group and polarity on the basic nitrogen in the side chain. In both normal and reversed phase modes the (+)-R-enantiomer eluted first in all of the analogs resolved. It can be concluded that: (1) substituents on the side chain did affect the interaction of the enantiomers with the polar carbamate moiety in the CSP; and (2) the dipole-dipole stacking between the π-donor 3,5-dimethylphenyl carbamate group pending from the glucose rings of the CSP and π-acceptor aryl group of the analyte is crucial for the efficient chiral discrimination. The chiral recognition mechanism(s) between these analogs and the chiral stationary phases are proposed. © 1996 Wiley-Liss, Inc.
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    Stereoselective metabolic pathways of ketoprofen in the rat: Incorporation into triacylglycerols and enantiomeric inversion (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 163-172 
    Details
    ISSN: 0899-0042
    Keywords: arylpropionic acid ; ketoprofen ; enantiomer ; stereoselectivity ; Coenzyme A thioester ; hybrid triacylglycerols ; inversion ; adipose tissue ; hepatocytes ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enantiomeric bioinversion of ketoprofen (KP) enantiomers and their incorporation into triacylglycerols were investigated in the rat (1) in vitro, using liver homogenates, subcellular fractions, and hepatocytes, and (2) in vivo, in different tissue samples after oral administration of the radiolabelled compounds. In liver homogenates or subcellular fractions, the enantiomer (S)-ketoprofen (S-KP) was recovered unchanged, whereas (R)-ketoprofen (R-KP) was partially converted into its Coenzyme A (CoA) thioester and inverted to S-KP. Both processes occurred mainly in the mitochondrial fraction. This supports the mechanism of inversion via stereoselective formation of CoA thioesters of R-KP, already described for other non-steroidal anti-inflammatory drugs. Incorporation into triacylglycerols was detected after incubation with intact hepatocytes in the presence of added glycerol. The process was stereoselective for R-KP vs. S-KP (covalently bound radioactivity 26,742 ± 4,665 dpm/106 cells vs. 6,644 ± 3,179 dpm/106 cells, respectively). However, no incorporation was found in liver samples after oral administration of either R-KP or S-KP. On the contrary, in adipose tissue samples a significant and stereoselective formation of hybrid triacylglycerols was observed: 11,076 ± 2,790 dpm.g-1 for R-KP vs. 660 ± 268 dpm.g-1 for S-KP. The incorporated R/S ratio, higher in adipose tissue (R/S = 17) than in hepatocytes (R/S = 4), indicates that fat may be the main tissue store for the xenobiotic R-KP in rats. © 1996 Wiley-Liss, Inc.
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    Enantiomeric separation of aminophosphonic acids by capillary electrophoresis (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 84-87 
    Details
    ISSN: 0899-0042
    Keywords: capillary electrophoresis ; aminophosphonic acid ; enantiomers ; osteoporosis ; cyclodextrin ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Racemic aminophosphonic acids were completely resolved into their enantiomers by capillary electrophoresis using β-cyclodextrin as a chiral selector in a borate electrolyte. The reproducibility of sample injection, solute migration time, and detection limits of the solute were studied. The calibration curve obtained from peak areas was linear over the concentration range of 10 to 300 μg/mL. © 1996 Wiley-Liss, Inc.
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    Capillary electrophoretic enantiomeric separations using the glycopeptide antibiotic, teicoplanin (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 88-107 
    Details
    ISSN: 0899-0042
    Keywords: teicoplanin ; glycopeptide antibiotics ; capillary electrophoresis ; enantioselectivity ; separation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Teicoplanin is the third in a series of macrocyclic glycopeptide antibiotics that has been evaluated as a chiral selector in capillary electrophoresis (CE). It was used to resolve over 100 anionic racemates at low selector concentrations. Like the other related glycopeptide antibiotics, its enantioselectivity tends to be opposite to that of the ansa-type antibiotics which prefers cationic compounds, particularly amines. Factors that affect teicoplanin-based enantioseparations include the selector concentration, pH, and the concentration of the organic modifier. The temperature and the nature and strength of the buffer are also known-to affect the stability of the chiral selector as well as the enantioseparation. Teicoplanin exhibited some features that were not noted with the other glycopeptide antibiotics. For example, it aggregates (forms micelles) in aqueous solutions and this influences its enantioselectivity. Unlike the other studied glycopeptides, teicoplanin precipitates in alcohol-water mixtures. It also binds less to the capillary wall than vancomycin as evidenced by the faster electroosmotic flow velocity. The micellization of teicoplanin is pH dependent so that the effect of pH on enantiorecognition is more complex for teicoplanin than for other chiral selectors. Also it is shown that the simple model proposed to explain the role of organic modifiers in cyclodextrin-based CE enantioseparations may not apply to these and other systems. © 1996 Wiley-Liss, Inc.
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    Chiral discrimination by HPLC on aryl carbamate derivatives of chitin coated onto microporous aminopropyl silica (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 131-135 
    Details
    ISSN: 0899-0042
    Keywords: polysaccharides ; optical resolution ; phase loading ; racemic compounds ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Optical resolution of a range of racemic compounds was investigated using bis(aryl carbamate) derivatives of chitin coated onto microporous organosilane-modified silica. The influence on chiral discrimination of factors such as the carbamate/support weight ratio, the nature of polysaccharide, and the influence of the aryl group substituents was investigated. The bis(3,5-dimethylphenyl carbamate) derivative of a noncommerical chitin gave the best results. © 1996 Wiley-Liss, Inc.
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    Significance of mobile phase composition in enantioseparation of chiral drugs by HPLC on a cellulose-based chiral stationary phase (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 136-142 
    Details
    ISSN: 0899-0042
    Keywords: enantioseparations ; high-performance liquid chromatography ; mobile phase modifier and additive ; cellulose-based CSP ; chiral acidic and basic drugs ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Eight randomly selected pharmaceuticals, which included ibuprofen, ketoprofen, albuterol, acebutolol, propafenone, betaxolol, methylphenidate, and homatropine, were directly separated on a cellulose tris(4-methylbenzoate) chiral stationary phase (CSP) without derivatization via normal phase mode HPLC. Enantioresolution was achieved by the optimization of the type and the ratio of mobile phase modifiers and additives. The modifiers included alcohols; the mobile phase additives were trifluoroacetic acid (TFA) and triethylamine (TEA). It was found that methanol and ethanol were superior to isopropanol as mobile phase modifiers for enhancing chiral separation of some of the chiral drugs. The results also demonstrated that TFA has a dominant effect on chiral separations for both acidic and basic chiral drugs, although for some basic drug such as homatropine, TEA was more beneficial at improving enantioseparation. The separation of acebutolol enantiomers was achieved for the first time by adding both TFA and TEA to the mobile phase. The purpose of this paper is to demonstrate that the applicability of cellulose based CSPs can be expanded by controlling the mobile phase compositions through the addition of trace amounts of achiral additives and the selection of the appropriate alcoholic modifier. © 1996 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
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  • 92
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    Electronic Resource
    Unusual amino acids VI. Substituted arylamino acids by asymmetric hydrogenation of N-Cbz and N-Boc protected dehydroamino acid derivatives (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 173-188 
    Details
    ISSN: 0899-0042
    Keywords: amino acids ; chiral rhodium complexes ; aminophosphine-phosphinite ; D- and L-enantiomers ; NMR spectra ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Substituted N-Cbz and N-Boc protected arylamino acrylic acids and esters have been prepared and used in asymmetric hydrogenations catalyzed by PROPRAPHOSRh. Stereoselectivities 〉 90% ee could be achieved, the rate of which is dependent on the position of the substituent in the aromatic ring. The N-Boc derivatives provide advantages compared with the N-Cbz analogues. The amino acid derivatives were fully characterized by 19F, 13C, and 1H NMR spectroscopy. © 1996 Wiley-Liss, Inc.
    Additional Material: 12 Tab.
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  • 93
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    Electronic Resource
    Design and development of chiral reagents for the chromatographic e.e. determination of chiral alcohols (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 397-401 
    Details
    ISSN: 0899-0042
    Keywords: chiral derivatization ; capillary GC ; capillary SFC ; diastereoisomeric esters ; optical resolution ; (S)-Trolox methyl ether ; primary alcohols ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: (S)-Trolox methyl ether is known as a powerful chiral reagent for the e.e. determination of chiral alcohols by separation of the corresponding diastereoisomeric esters on achiral GC and SFC columns. In order to further improve his methodology, five possible candidates resultings from variation of structural elements of parent reagent have been tested for derivatization with selected alcohols and subsequent analysis of the diastereoisomeric pairs of esters. The results of this optimization procedure showing the ways to new potent reagents are discussed. © 1996 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
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  • 94
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    Stereoselective pharmacokinetics of [14C]-labeled KE-298, a new anti-rheumatic drug, in rats (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 258-263 
    Details
    ISSN: 0899-0042
    Keywords: stereoselectivity ; radioactivity ; distribution ; hepatocytes ; metabolism ; protein binding ; analbuminemic rats ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The stereoselective pharmacokinetics of two enantiomers of [14C]-labeled KE-298 [2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanonic acid] were investigated in rats. The blood levels of radioactivity after the oral administration of (+)-(S)-[14C]KE-298 were higher than that for (-)-(R)-[14C]KE-298; the AUC of the former was approximately twice that of the latter. No significant stereoselectivity was observed in absorption rate. The tissue/plasma level ratios at 30 min after oral administration of (-)-(R)-[14C]KE-298 in the liver and kidney, the major metabolic and/or excretory organs, were 2 to 3 times higher than those for (+)-(S)-[14C]KE-298. Neither was evidence of stereoselectivity found in the excretion of radioactivity. During incubation with isolated rat hepatocytes in vitro, the metabolic rates of KE-298 enantiomers were not significantly different. Plasma protein binding 30 min after the oral administration of (+)-(S)-[14C]KE-298 and (-)-(R)-[14C]KE-298 was 99.3% and 97.0%, respectively. Comparing the unbound fraction, (-)-(R)-[14C]KE-298 was approximately 4 times higher than (+)-(S)-[14C]KE-298. In order to make clear the relationship between stereoselective pharmacokinetics and protein binding for [14C]KE-298, the comparative pharmacokinetics of (+)-(S)-[14C]KE-298 and (-)-(R)-[14CC]KE-298 were investigated in analbuminemic rats. In these animals, no evidence of stereoselectivity was found for either blood level-time profiles or plasma protein binding. These results revealed that the stereoselective pharmacokinetics of KE-298 in rats might be due to enantiomeric differences in binding to plasma albumin. © 1996 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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  • 95
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    Electronic Resource
    Masthead (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996) 
    Details
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/chir.530080301
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  • 96
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    Sulfated cyclodextrins for the chiral separations of catecholamines and related compounds in the reversed electrophoretic polarity mode (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 316-324 
    Details
    ISSN: 0899-0042
    Keywords: sulfated cyclodextrin ; catecholamine ; chiral ; CZE ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The utility of negatively charged sulfated cyclodextrins (SCD) as chiral additives (CA) in capillary electrophoresis (CE) was studied in the chiral resolution of several compounds of pharmaceutical interest, including catecholamines such as norepinephrine, epinephrine, DOPA and their precursors, phenylalanine, and tyrosine. Experiments were conducted using 10 mM sodium phosphate monobasic solution and 2% SCD adjusted to pH 3.2 with phosphoric acid. Chiral recognition mechanisms were explored using structurally related analytes including basic, acidic, and neutral compounds as well as 3,5-dinitrobenzoyl phenylglycine, phenylalanine, and homophenylalanine. The advantage of the reversed electrophoretic polarity mode for the enantioresolution of these compounds is also discussed. © 1996 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
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  • 97
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    Electronic Resource
    Detailed experimental and theoretical analysis of chiral discrimination: Enantioselective binding of R/S methyl mandelate by β-cyclodextrin (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 341-350 
    Details
    ISSN: 0899-0042
    Keywords: chiral discrimination ; β-Cyclodextrin ; complexation ; enantiodiscrimination ; computational chemistry ; molecular modeling ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Enantiodifferentiation of methyl mandelate by β-Cyclodextrin in the liquid phase is explored in detail. Temperature dependent studies using a β-cyclodextrin chiral stationary phase provided differential binding enthalpies and entropies. NMR studies revealed where around the host molecule the guest tends to reside. Molecular dynamics simulations correctly predict the retention order and provide an atomistic account of how chiral discrimination takes place. It is found that short range dispersion forces rather than long range coulombic forces are responsible for both complexation and for enantiodiscrimination. The intermolecular hydrogen bonds are not discriminating and the idea that a tight fit of included species within a cyclodextrin cavity be a requirement for chiral discrimination is questioned. © 1996 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
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  • 98
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    Electronic Resource
    Masthead (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996) 
    Details
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/chir.530080401
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  • 99
    Electronic Resource
    Electronic Resource
    Masthead (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996) 
    Details
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/chir.530080701
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  • 100
    Electronic Resource
    Electronic Resource
    New method for the resolution of the enantiomers of 5,6-Dihydroxy-2-Methyl-Aminotetralin by selective derivatization and HPLC analysis: Application to biological fluids (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 381-389 
    Details
    ISSN: 0899-0042
    Keywords: aminotetralin ; catechol group ; homochiral derivatization ; (+)-(R)-1-phenylethyl isocyanate ; enantiomers ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A new chiral derivatization procedure for the HPLC resolution of chiral catecholamines and structurally related compounds is described. The homochiral reagent, (+)-(R)-1-phenylethyl isocyanate (RPEIC), was added to separate and quantitate the enantiomers of rac-5,6-dihydroxy-2-methyl-aminotetralin, the main metabolite of rac-5,6-diisobutyryl-2-methyl-aminotetralin, a potent dopamine agonist, by reversed-phase HLPC analysis. To avoid catecholamine degradation in the basic reaction medium and to obtain the selective and quantitative derivatization of the amino group of the compound, the reversible complex formation between diphenylborinic acid (DPBA) and the catechol group, in alkaline medium, was performed before homochiral isocyanate addition. The RPEIC derivatization was completed in 30 min and then the DPBA complex was dissociated by adding dilute acid. The structure of intermediates and urea derivatives was confirmed by mass spectrometry. The use of an electrochemical detector, operating in redox mode, allowed HPLC quantitation of enantiomers at the nanogram level in plasma and urine. The derivatization procedure is also suitable for other catecholamine-related compounds. © 1996 Wiley-Liss, Inc.
    Additional Material: 10 Ill.
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