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  • 1995-1999  (982)
  • 1980-1984
  • 1996  (982)
  • Cell & Developmental Biology  (458)
  • Chemical Engineering  (437)
  • 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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    Stereoselective disposition of flurbiprofen from a mutual prodrug with a histamine H2-antagonist to reduce gastrointestinal lesions in the rat (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 494-502 
    Details
    ISSN: 0899-0042
    Keywords: hydrolysis ; carboxylesterase ; bioconversion ; plasma concentration ; pharmacokinetics ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The in vitro and in vivo stereoselective hydrolysis characteristics of the mutual prodrug FP-PPA, which is a conjugate of flurbiprofen (FP) with the histamine H2-antagonist PPA, to reduce gastrointestinal lesions induced by FP were investigated and compared with those of FP methyl ester (rac-FP-Me) and FP ethyleneglycol ester (rac-FP-EG). The rac-FP derivatives were hydrolyzed preferentially to the (+)-S-isomer in plasma and to the (-)-R-isomer in liver and small intestinal mucosa. Interestingly, in the gastric mucosa, the stereoselectivity of hydrolysis of (-)-R-FP-PPA was opposite from that of rac-FP-Me and rac-FP-EG, which suggested that the stereoselective hydrolysis of FP-PPA was helpful in reducing gastric damage induced by (+)-S-FP. However, hydrolysis of all rac-FP derivatives was found to be catalyzed by carboxylesterases in the gastric mucosa. The stereoselective disposition of FP enantiomers early after intravenous administration of rac-FP-PPA could be explained by the stereoselective formation of (-)-R-FP from rac-FP-PPA in the liver. (-)-R-FP-PPA was completely hydrolyzed to form (-)-R-FP in vivo, while 78% of (+)-S-FP-PPA was hydrolyzed to (+)-S-FP, with a corresponding decrease in the area under the curve. Twenty-five percent of (+)-S-FP-PPA might be eliminated as the intact prodrug or its metabolites other than FP. The most important bioconversion of FP-PPA occurred in plasma, and additional hydrolysis of the R-enantiomer in liver resulted in the stereoselectivity observed following both i.v. and p.o. administration. © 1996 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
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    Characterization of fluid distributions in porous media by NMR techniques (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 538-546 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Nuclear magnetic resonance (NMR) spin-lattice relaxation measurements are used to investigate pore structures and fluid phase distributions in porous media. A new method for estimating relaxation time distribution functions from measured relaxation data is presented using a B-spline basis to represent the distribution function and Tikhonov regularization to stabilize the estimation problem. Surface relaxivity, which is required to convert relaxation time distributions to pore-size distributions of fluid phase distributions at partial saturations, is determined using pore volume-to-surface-area ratios estimated by NMR diffusion measurements. This approach was validated by analyzing certain model porous media with known pore volume-to-surface-area ratios. The method is demonstrated by determining pore-size and fluid phase distributions of sandstone and carbonate samples, as well as by comparing the pore-size distributions of chalk samples obtained by this methodology with those estimated by mercury porosimetry.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420223
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    A new solution to emulsion liquid membrane problems by non-Newtonian conversion (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 547-561 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Emulsion liquid membrane separation processes remain excessively vulnerable to one or more of four major problems. Difficulties lie in developing liquid membranes that combine high levels of both stability and permeability with acceptably low levels of swelling and ease of subsequent demulsification for membrane and solute recovery. This article provides a new technique for simultaneously overcoming the first three problems, while identifying physical indications that the proposed solution may have little adverse effect on the fourth problem (demulsification) and may even alleviate it. Numerous benefits of optimized conversion of the membrane phase into suitable non-Newtonian form are identified, their mechanisms outlined, and experimental verifications provided. These include increased stability, retained (or enhanced) permeability, reduced swelling, increased internal phase volume, and increased stirrer speeds. The highly favorable responsiveness of both aliphatic and aromatic membranes to the new technique is demonstrated.
    Additional Material: 18 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420224
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    Masthead (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996) 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420301
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    Phase equilibria and volumetric properties of aqueous CACl2 by an equation of state (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 585-594 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A comprehensive equation of state was developed to represent the phase equilibria and volumetric properties of aqueous calcium chloride solutions at temperatures above 523 K. The equation consists of a reference part and a perturbation contribution. The reference function is developed from the statistical mechanical theory for mixtures of dipolar and quadrupolar hard spheres, which agrees well with the Monte Carlo simulation results. In this treatment, calcium chloride is described by the completely undissociated model. The empirical perturbation function is a truncated series of virial expansion terms. Thus, mixing rules are guided by those of virial coefficients, which are derived rigorously from statistical mechanics. The equation reproduces experimental saturated vapor pressures and volumetric data within experimental uncertainty for temperatures to 623 K. At higher temperatures, few and less accurate experimental data are available, but values of the saturated vapor pressures of the liquid have been reported and are represented satisfactorily.
    Additional Material: 12 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420227
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    Dynamic contact angles and flow in vicinity of moving contact line (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 601-612 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A previously developed mathematical wetting model is generalized and applied to the following two closely related situations: the spreading of a liquid over a prewet solid surface and the receding contact-line motion with a microscopic residual film, remaining behind the contact line. An analytical expression for the velocity dependence of the dynamic contact angle is derived. Macroscopic characteristics (the dynamic contact angle and drag force) and the flow field corresponding to the spreading of a liquid over a wet solid surface differ considerably from those calculated for a dry surface. Under certain conditions the flow in the reference frame fixed with respect to the contact line has a region with closed streamlines. The region appears due to the flow-induced Marangoni effect, the reverse influence of the surface tension gradient along the liquid-solid interface caused by the flow on the flow, which gives rise to the gradient. The results are compared qualitatively with experimental data.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420302
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    Forces on a large cylindrical bubble in an unsteady rotational flow (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 638-648 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The full Navier-Stokes equations were employed with a single-fluid model and a front tracking scheme to study a large cylindrical bubble in a free shear layer. A general formulation based on work by Auton et al. of the hydrodynamic forces on a finite Reynolds number large bubble in an unsteady, nonuniform and rotational flow was then used to investigate the effects of nonlinear spatial and temporal gradients on dispersion. The resulting bubble dispersion in the full Navier-Stokes solution significantly differ from that by a conventional bubble dynamic equation based on linear spatial gradients and quasi-steady flow. This was due to the adjunct forces not accounted for by such a formulation, which are related to regions of high nonuniformity and unsteadiness. These adjunct forces in the drag/lift direction were correlated with rapid variations of relative bubble velocity and high gradients of the liquid velocity.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420305
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    Leveling of a film with stratified viscosity and insoluble surfactant (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 623-637 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The evolution of a film with insoluble surfactant on a wavy horizontal wall differs from flow without surfactant (the way it usually is studied) in that the film passes through different stages. The first stage is as if the surfactant were absent. Once the surface tension gradient - induced by the nonuniform surfactant concentration adsorbed at the free surface - starts resisting the flow effectively, the evolution enters a transitional stage. A final stage is reached once the free surface becomes rigid due to the surface-tension gradient (high elasticity limit) or becomes virtually leveled before the surface-tension gradient is released (low elasticity limit). The velocity profile through the film changes with time, sol fluid is depleted or accumulated at different strata in the film as the flow evolves. The velocity profile and resulting deformations throughout the film can be influenced significantly by the viscosity distribution or stratification, which occurs, for example, when multiple layers of different viscosity are coated simultaneously. A model and applications for the leveling of such a film are presented. The evolution is described in general terms for a film of uniform viscosity and for a film of two discrete layers of different viscosity. Then the three limiting cases are established. For two of these limits, the effect on the exponential decay rate of the flow and the deformation of the different strata or layers is examined when the viscosity is changed in an infinitesimally thin layer or stratum, and in a layer of finite thickness in films of two and three discrete layers.
    Additional Material: 9 Ill.
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    URL: http://dx.doi.org/10.1002/aic.690420304
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    Adsorption of associating molecules in micropores and application to water on carbon (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 809-819 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A general theory for the adsorption of self-associating molecules in microporous structures is developed. The approach is similar to the “chemical” interpretation of nonideality of vapor and liquid phases. The theory displays Type 5 isotherm behavior and can explain Types 1 and 5 transition. Isothermal data are represented by only three parameters: Henry's law constant, saturation capacity, and reaction constant for “cluster” formation in the micropores. When isotherms at different temperatures are available, the theory can be used with five temperature-independent parameters to describe the entire phase behavior including the heat of adsorption. Water adsorption on activated carbon, the most common display of Type 5 behavior, is used to test the theory. Analysis of several data sets indicates that the theory can closely correlate data, provide physically meaningful parameter values in line with carbon properties, and it is highly effective in correlating temperature variation. The reaction enthalpy for water dimerization in the carbon micropores is lower than that in vapor phase. This preliminary conclusion with the theory needs to be supported with more accurate data when available.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420319
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    MRI investigations of fractures and multiphase flow in fractured media (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 820-828 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The new application of nuclear magnetic resonance imaging (MRI) techniques for characterizing fractures and flow in fractured media is investigated. Specifically, a relaxation-weighted imaging technique is used for selectively highlighting either fracture or porous matrix regions. Many advantages over conventional spin-density MRI techniques for characterizing fractured media are demonstrated. Its use to speed image acquisition is also demonstrated. In addition, a multislice profile imaging technique is used to investigate imbibition and drainage displacement experiments in fractured porous media. These images demonstrate that the fractures can have profound effects on the fluid distributions in multiphase flow.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420320
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    Model of crystallization in a confined space applied to iron uptake and release by ferritin (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 829-836 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Many living organisms store iron in solid form, Fe(III), as a crystal in the inner cavity of the ferritin molecule. When iron is needed for biosynthesis, a reducing agent reduces Fe(III) into the soluble form Fe2+ released by ferritin. Crystallization and release processes are reversible, and their rates evolve in an identical way as a function of the number n of iron atoms in the molecule. The rate increases with n, showing a maximum value when n is approximately 1,300, and then stabilizes for the highest values of n, which can reach 4,500. On the other hand, plotting the amount of released iron as a function of time gives curves with a sigmoid shape. The proposed model was based on the theoretical description of different steps involved in crystal growth inside the protein shell: several independent crystals grow freely at the inner protein wall, and then a distribution function takes into account possible overlapping of different crystallite clusters, whose further growth is limited by diminution of the available space inside the cavity. The kinetics derived was then used to calculate the release curve as a function of time. Solving the system of differential mass-balance equations was simplified by describing the ferritin population as a large discrete distribution of species. The model fully fitted and explained the variation in the crystallization rate with n, and the sigmoid shape of the release curve as a function of time obtained experimentally in a thin-layer electrochemical cell.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420321
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    Prediction of polymer-solvent phase equilibria by a modified group-contribution EOS (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 837-849 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A new group-contribution lattice-fluid equation of state (GCLF-EOS), which is capable of predicting the equilibrium properties of polymer-solvent solutions, was developed by modifying the original GCLF-EOS of High and Danner. The GCLF-EOS is a group-contribution form of the Panayiotou-Vera equation of state based on the lattice-hole theory. Group contributions for the interaction energy and reference volume were developed based only on the saturated vapor pressure and liquid densities of low molecular weight compounds. For a mixture, a binary interaction parameter was introduced into the mixing rules. Group contributions for the binary interaction parameter were developed from the binary vapor-liquid equilibria of low molecular weight compounds. This modified GCLF-EOS model gives excellent predictions of solvent activity coefficients both at infinite dilution and at finite concentrations. It is significantly better than the original GCLF-EOS model in its prediction capability. The only input required for the model is the structure of the molecules in terms of their functional groups. No other pure component or mixture properties of the polymer or solvent are needed.
    Additional Material: 13 Ill.
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    URL: http://dx.doi.org/10.1002/aic.690420322
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    Measurement and correlation of ion activity in aqueous single electrolyte solutions (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 249-258 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Ion-selective electrodes were used to measure the activity coefficients at 298.2 K of individual ions in aqueous solutions of NaCl and NaBr up to of 5 molal and of KCl up to 4 molal. The mean ionic activity coefficients of NaCl, NaBr, and KCl, obtained from the values of the activity coefficients of the individual ions, show good agreement with values reported in the literature. The experimental results show that the activity coefficients are different for the anion and the cation in an aqueous solution of a single electrolyte and that, as expected from the ion-ion and ion-solvent interactions, the activity coefficient of an ion depends on the nature of its counterion. A modified form of the Pitzer's model, which distinguishes between the activity coefficients of the anion and the cation, was used to correlate the experimental results.
    Additional Material: 8 Ill.
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    URL: http://dx.doi.org/10.1002/aic.690420121
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    Effects of mixing on the composition and morphology of tissue-engineered cartilage (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 850-860 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Cartilage constructs were grown using isolated chondrocytes and biodegradable polymer scaffolds made of fibrous polyglycolic acid in the form of 1-cm-dia × 5-mm-thick discs. The scaffolds were seeded in a mixed cell suspension and cultured for up to 8 weeks under static or mixed tissue culture conditions in petri dishes and spinner flasks. Turbulent mixing significantly improved the biochemical compositions and altered morphologies of the cartilage constructs, which were the thickest ones cultured to date in vitro. Constructs from mixed cultures were more regular in shape and contained up to 70% more cells, 60% more sulfated glycosaminoglycan, and 125% more total collagen when compared to constructs from static cultures. Mixing also induced the formation of an outer capsule with multiple layers of elongated cells and collagen fibrils around the inner tissue phase, while statically grown constructs consisted of round cells embedded in cartilaginous matrix. Mixing during cell seeding and tissue culture is thus an important parameter for the cultivation of tissue-engineered cartilage in a range of sizes, shapes and compositions for a variety of clinical applications (e.g., fibrous cartilage for reconstructive surgery or articular cartilage for joint resurfacing).
    Additional Material: 7 Ill.
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    URL: http://dx.doi.org/10.1002/aic.690420323
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    Mathematical modeling of a solid-state limiting current carbon monoxide sensor (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 876-883 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A solid-state carbon monoxide sensor was fabricated using a 9% yttria-stabilized zirconia (YSZ) disc sandwiched between two platinum thin-film electrodes. One of the electrodes was coated with a thin layer of 7 CuO · 10 ZnO · 3 Al2O3 catalyst. The sensor showed limiting current behavior at an applied voltage between 0.5 and 1.2 V. Linear response was observed with carbon monoxide in a nitrogen-oxygen mixture at high temperature and limiting current conditions. The linear carbon monoxide concentration range increased with increase in the operating temperature and its sensitivity increased from 2.437 mA · atm-1 CO at 1,023 K to 10.771 at 1,093 K. These characteristics were adequately described by the proposed mathematical model relating the response to the rate processes occurring in the catalyst layer and in the electrochemical cell under limiting current conditions. The model showed that effective sensing and high sensitivity are best obtained using a catalyst with high catalytic activity toward the test solute and proper design and fabrication of the sensor to ensure its high diffusivity in the catalyst.
    Additional Material: 8 Ill.
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    URL: http://dx.doi.org/10.1002/aic.690420325
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    Stochastic dynamic solution of nonlinear differential equations for transport phenomena (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 889-891 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420327
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    Chlorinated organics removal from water by plasma-graft filling polymerized membranes (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 892-895 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420328
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    Absorption of water vapor into LiBr solutions with 2-ethyl-1-hexanol (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 884-888 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420326
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    Role of surface fines on growth rate of L-SCMC crystals in DL-SCMC aqueous solution (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 896-900 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420329
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    Masthead (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996) 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420401
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    Fickian diffusion in binary mixtures that form two liquid phases (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 910-920 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: New data on the variation of the diffusion coefficient with concentration in binary nonideal liquid mixtures are presented. The diffusion coefficients were measured with laser holography with an improved analysis procedure and are primarily in systems that form two liquid phases. The results show that for such systems the diffusion coefficient is constant if a chemical-potential driving force is used. If, however, the miscibility gap is wide, the Schreiner equation (Schreiner, 1922) is shown to be more accurate than relations that consider the variation of viscosity. Cluster theories developed for diffusion behavior near critical points were found to explain the data well only in water-organic systems on the water-rich side.
    Additional Material: 11 Ill.
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    URL: http://dx.doi.org/10.1002/aic.690420403
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    Dry superconducting magnetic cleaning of pulverized coal (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 277-284 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420126
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    Uniqueness and multiplicity in isothermal CMSMPR crystallizers (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 285-289 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420127
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  • 73
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    Spatiotemporal patterns in catalytic reactors (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1041-1068 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The study of spatial structures in heterogeneous reactors is a challenging academic topic, revealing patterns that differ from those known to exist in reaction-diffusion systems exposed to uniform conditions, as well as a practical problem that should affect design and operation procedures of commercial reactors like the catalytic convertor. Experimental observations and mathematical models of spatiotemporal patterns in high-pressure catalytic reactors are reviewed. Patterns in high-pressure reactors, in which thermal effects provide the positive feedback, as well as the long-range communication, usually emerge due to global interaction. Patterns are classified comprehensively by considering reactors of increasing degree of complexity: a wire or ribbon exposed to uniform conditions, a globally coupled catalyst in a mixed reactor or in a control loop, and a fixed bed in which interaction by convection occurs only in one direction. Catalytic wires are not expected to exhibit sustained patterns in the absence of global interaction. Global interactions by external control or gas-phase coupling are shown experimentally and analytically to induce a rich plethora of patterns. Complex motions were simulated to occur due to the interaction of convection, conduction and reaction in a fixed-bed; only a few of these patterns were experimentally observed. Directions for future research are suggested.
    Additional Material: 26 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420416
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  • 74
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    Stability of the ignited state in packed-bed reactor (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1088-1094 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The ignited state is associated with a thin reaction zone and a steep temperature gradient ahead of the front. The stability of this front is analyzed for small radial and azimuthal perturbations. The near-equidiffusional assumption is made, and the deviation of the Lewis number from unity is considered as the bifurcation parameter. The analysis shows that the planar front becomes unstable at Lewis numbers above unity after a Hopf bifurcation. The oscillatory front collapses into hot spots or rings which oscillate around the axial axis. For Lewis numbers less than one, a steady-state cellular front structure is found.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420419
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  • 75
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    Reactor of vapor-phase graft polymerization of reactive monomer onto porous hollow fiber (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1095-1100 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A novel reactor for the modification of a porous hollow-fiber membrane up to 1 m in length is presented. The polyethylene hollow fiber irradiated with an electron beam was exposed to the vapor of an epoxy-group-containing vinyl monomer (glycidyl methacrylate) in a cylindrical reactor rotated at 1 rpm. Construction of the hollow fibers resulted in a diffusion-controlled reaction system, which led to the nonuniformity of degree of grafting (dg), whereas the shuffling of the hollow fibers by rotating the cylindrical reactor provided a higher reactivity (dg = 110% for 100 min at 300 K) and uniformity (standard deviation = 4.5%) of dg.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420420
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  • 76
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    Drying with internal heat generation: Theoretical aspects and application to microwave heating (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 359-368 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A model of simultaneous heat and mass transfer presented describes drying with internal heat generation. Since a liquid expulsion phase is observed, a numerical procedure was developed to account for saturated and unsaturated zones and to model the liquid expulsion. The model was validated by a drainage experiment. An experimental rig was built to conduct microwave drying experiments in well-controlled conditions using capillary porous body (light concrete) as test material. Two types of drying (high and low power) were distinguished, depending on whether or not boiling occurred in the sample. The heat source term in the medium was determined from the experimental results. The numerical results agree with the experimental observations in terms of drying kinetics and transfer mechanisms. This allows a very accurate description of the transport phenomena and the liquid expulsion phase associated with high-power drying.
    Additional Material: 13 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420206
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  • 77
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    Backone family of equations of state: 1. Nonpolar and polar pure fluids (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1116-1126 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The Helmholtz energy F is written as the sum F = FH + FA + FPol, where FH is the hard-body contribution, FA the attractive dispersion force contribution, and FPol either the quadrupolar or dipolar contribution. Here, a new expression for FA is constructed by a simultaneous correlation of experimental data of methane, oxygen, and ethane. The resulting equations for F with only three or four substance-specific parameters are tested for several nonpolar, quadrupolar, and dipolar fluids. In the correlation of large data sets good results are obtained. The significance of the approach, however, is in the good to excellent prediction of all thermodynamic properties in the whole fluid region based on a parameter fit to only four experimental data - two vapor pressures and two saturated liquid densities.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420423
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  • 78
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    Laboratory batch reactor method for kinetic study of chemical vapor deposition (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1108-1115 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A lab-scale nonflowing reactor was built to study chemical vapor deposition reactions. Mass spectrometry is used to follow reaction pathways and to determine instantaneous reaction rates throughout film growth. In each experiment, the kinetic rate dependence on concentration for a wide range of concentrations is observed as reactants convert to products. This method of obtaining kinetic data is efficient in terms of sample loading, gas usage, and time, since over 200 instantaneous rate/composition pairs can be determined from one 30-min deposition. Because the rate is determined from gas-mass balance, rather than film-thickness measurements, an unlimited number of rate studies can be made on one sample. As a test case, the SiH4 reduction of WF6, used to deposit tungsten during integrated-circuit production, was investigated in the 0.64-L nonflowing laboratory reactor. Gas compositions were measured 2 mm from the growing surface, throughout time, with a mass spectrometer equipped with a capillary sampling tube. Tungsten was deposited on the 95°C surface, and SiHF3 was the primary silicon fluoride reaction product for most tested conditions. A multiple-regression analysis of 1,975 instantaneous composition/rate pairs gives orders of 1.22 in silane, 0.27 in hydrogen, and -2.17 in WF6. The ratio of SiF4 to SiHF3 stays low and constant until the gas becomes silane-rich. The evolution of the instantaneous rate over time implies that a minimal level of thermal activation of the reactive gases is necessary for the deposition to be surface-rate-limited. Preliminary heat-transfer models of the wire substrate imply that heat transfer to the gas phase is in the Knudsen regime.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420422
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  • 79
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    Air purification in a reverse-flow reactor: Model simulations vs. experiments (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1139-1148 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The behavior of a reverse-flow reactor was studied for the purification of polluted air by catalytic combustion. A heterogeneous one-dimensional model was extended with a heat balance for the reactor wall. An overall heat transport term is included to account for the small heat losses in radial direction.The calculations are compared to experimental data without using fit parameters. The agreement between simulations and experiments is generally good. Discrepancies can be explained mainly by inaccurate kinetic data and experimental uncertainties. At low gas velocities and for small reactor diameters, the one-dimensional model failed and a two-dimensional model must be developed to improve the predictive potential.
    Additional Material: 13 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420425
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  • 80
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    Conditional statistics in turbulent scalar mixing and reaction (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1149-1152 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: No Abstarct.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420426
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  • 81
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    Analysis of cell-target encounter by random filopodial projections (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1127-1138 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Dynamic projections from the surface of many motile cell types provide for variable contact with the extracellular environment and can be important in regulating cell migration events. For example, during nerve development and regeneration, the sensory motile tip of the axon exhibits long, slender filopodia projecting from the growth cone periphery. Extension and retraction of these filopodia continually remodel the points of contact between axon and surroundings. Experimental studies show that filopodial contact with specific extracellular features can guide subsequent growth cone migration, suggesting a potentially important means of engineering nerve growth to repair nerve injury or construct biological neural networks. A simulation model is presented of the dynamic filopodial structure on the nerve growth cone based on recent experimental characterization. The model is analyzed to obtain quantitative relationships between average filopodial characteristics, which are commonly measured experimental quantities, and the underlying parameters of individual filopodium dynamics. It is then applied to simulate encounter between a growth cone and its target due to filopodial dynamics alone. Filopodial contribution to growth cone-target encounter is summarized in terms of a mean encounter time that is reminiscent of a first passage time for a diffusing particle. The parametric relationships in this study provide a basis for further investigation of filopodial-mediated mechanisms in nerve growth and other cellular processes.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420424
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  • 82
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    Influence of wall roughness on the hydrodynamics in a circulating fluidized bed (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1153-1156 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420427
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  • 83
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    Use of Taylor dispersion for the measurement of probe diffusion in polymer solutions (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1157-1163 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420428
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  • 84
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    Apparent size-dependent growth of potash alum crystals by agglomeration (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1170-1173 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420430
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  • 85
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    Robust Smith-predictor controller for uncertain delay systems (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1033-1040 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Necessary and sufficient conditions for the robust stability and performance of the Smith-predictor controller, modeled under a norm-bounded uncertainty, are given in a general formulation. In addition, a practical stability condition is obtained as a special corollary of the main results. These conditions provide useful and practical guidelines for the development of a systematic robust design method. In particular, an application is developed for the robust control of first-order deadtime systems with simultaneous uncertainties in all three parameters of the model. A simulation example and the results of a case study on the robust level control of a coupled-tanks apparatus are provided for illustration.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420415
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  • 86
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    Reduction of the wall effect in a packed bed by a hemispherical lining (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1181-1186 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420432
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  • 87
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    Gas-solid mass transfer in a jetloop reactor (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1187-1190 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420433
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  • 88
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    Electronic Resource
    Output-feedback control of nonlinear plants (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 2540-2554 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: For multiinput-multioutput nonlinear plants whose state-feedback control problem is solvable with complete or partial output linearization, the output-feedback problem is addressed by combining the state-feedback controller with a suitable closed-loop state inferer (detector). A candidate closed-loop detector was built to study the stability of the resulting plant-controller interconnection. As a result, sufficient conditions for closed-loop asymptotic nominal stability, as well as a systematic and simple design-tuning procedure, are obtained. The stabilization of an open-loop, unstable, free-radical homopolymerization reactor was studied as an application example.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420914
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  • 89
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    Gas holdup in bubble column reactors operating in the churn-turbulent flow regime (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 2627-2634 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A comprehensive experimental study of gas holdup in bubble columns of varying diameters, fitted with different distributor types, using several liquids is presented. Air was used as the gas phase. Experiments to test the influence of gas density were also carried out with He, Ar, and SF6. A generalization of the two-phase model for gas-solid fluidized beds was used to interpret the experimental data where the “dilute” phase is identified with the “large” bubble population and the “dense” phase with the liquid phase where the “small” bubble population is entrained. Gas holdups in dilute and dense phases were determined from dynamic gas disengagement experiments.In the churn-turbulent regime of operation, voidage of the gas in the dense phase was independent of the superficial gas velocity. Reilly et al.'s correlations for the gas holdup and superficial gas velocity at the regime transition point estimate the gas voidage of the dense phase and the superficial gas velocity well through this phase. Corresponding correlations of Wilkinson et al. significantly underpredict dense-phase parameters. The experiment showed that the dilute phase or large bubble holdup in bubble columns, operating at superficial gas velocities 〉 0.1 m/s, is independent of liquid properties, how the gas is distributed and the density of the gas phase. But it is affected significantly by the column diameter. Relying on hydrodynamic analogies with a gas-solid-fluid bed, a simple correlation was developed that is considerably more accurate than the Wilkinson correlation that significantly overpredicts large bubble holdup.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420923
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  • 90
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    Model for the reaction-rate-limited dissolution of solids with Etch-rate heterogeneities (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 2654-2660 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The coalescence of isotropic etch pits observed in the dissolution of semiconductor substrates is studied using a discrete model for the evolution of the surface under reaction-rate-limited conditions. The model discretizes the solid into cubic elements and repetitively applies dissolution rules to the individual elements. The rate of mass removal is based on the number and arrangement of the element's exposed faces and the specified reaction-rate parameters. Detailed knowledge of the surface normal is not required. The model shows that even at moderate etch pit densities, the effects of the coalescence do not significantly alter the trends observed for noncoalescing etch pits.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420926
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  • 91
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    Autotuning for model-based PID controllers (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 2687-2691 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420930
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  • 92
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    Holdup and solvent extraction characteristics in electrostatic liquid-liquid contactor (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 2683-2686 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420929
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    Electrochemical process engineering: A guide to the design of electrolytic plant. By F. Goodridge and K. Scott, Plenum Press, 1995, 312 pp., $59.50 (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 2698-2698 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420932
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  • 94
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    PDF modeling of turbulent-mixing effects on initiator efficiency in a tubular LDPE reactor (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 2926-2940 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The effect of turbulent mixing in the reaction zone of a tubular low-density polyethylene reactor was studied by combining a Lagrangian composition probability density function (LCPDF) code with a computational fluid-dynamics code. Because the LCPDF code can treat the chemical reaction terms in a turbulent flow without resorting to moment closures, it is used to describe the temperature and scalar fields of reactants including initiator and monomer molar concentrations, and the moments of the molecular weight distribution. The chemical reaction terms are efficiently dealt with using a three-parameter chemical lookup table that contains the temperature and composition changes as functions of initiator and monomer concentrations and temperature over a small time step. The reaction-rate constants from the study of Lee and Marano (1979) are functions of temperature and pressure. The flow fields are obtained using the k - ε turbulence model. Because the temporal and spatial evolution of all fields in the reactor can be simulated, it is possible to study the effect of the initiator injection location, flow rate and temperature of the monomer and initiator feed streams on polymerization in considerable detail. Moreover, by observing the probability distribution of the composition fields, a better understanding of hot-spot formation is achieved, leading to improved reactor designs.
    Additional Material: 15 Ill.
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    URL: http://dx.doi.org/10.1002/aic.690421020
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  • 95
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    Particles flow pattern and local heat transfer around tube in moving bed (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1621-1626 
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    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Flow visualization of flowing particles around a tube of various types of tube arrangements in a moving bed was studied using X-ray video films to obtain a relation between particles behavior and local heat-transfer coefficients. A stagnant part of solid particles was observed on the tube in the case of a staggered arrangement. This part did not appear in the case of the single tube and the single row of tubes. The measured local heat-transfer coefficients around a tube was decreased in this stagnant part. Furthermore, influences of different tube arrangements both on flow patterns of particles and on local heat-transfer coefficients between tubes and bed were examined.
    Additional Material: 13 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420613
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  • 96
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    Statistics of multiple particle breakage (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1600-1611 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A method for generating theoretical breakage distribution functions for multiple particle breakage is presented. It starts with the joint probability function that accounts for all the child particles; it is then reduced to the marginal probability function commonly used in the breakage equation. This method is flexible enough to allow the user to choose the number of child particles and the functional form to be used. The method is demonstrated with both product and summation functions with a power-law form. To facilitate the use of these theoretical functions for statistical analyses, a companion discretized breakage equation is developed. The new equation guarantees the conservation of mass and correct prediction of the total number of particles despite discretization. It is easy to use because it is a set of ordinary differential equations and applicable to both equal-size and geometric-size intervals. Simulation results show that different breakage distribution functions coupled with different breakage rates can produce almost indistinguishable particle-size distributions, signifying the need for further work in this area.
    Additional Material: 10 Ill.
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    URL: http://dx.doi.org/10.1002/aic.690420611
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  • 97
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    Coagulation and fragmentation: Universal steady-state particle-size distribution (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1612-1620 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A population balance model presented describes simultaneous coagulation and fragmentation during shear-induced flocculation. Given sufficient time, a floc-size distribution reaches steady state that reflects the balance between coagulation and fragmentation. The model agrees with experimental data for the evolution of the average floc size. Higher shear shifts the steady-state size distribution to smaller sizes. When the steady-state size distributions obtained at various shear rates are scaled with the average floc size, however, they collapse onto a single line. This indicates that the steady-state floc-size distribution is self-preserving with respect to fluid shear. This distribution is universal for the employed coagulation and fragmentation rates provided that less than 5% (by number) of the particles remain unflocculated. This result is supported with experimental data on shear-induced flocculation of polystyrene particles, although a detailed quantitative comparison is limited by the irregular structure of the flocs.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420612
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  • 98
    Electronic Resource
    Electronic Resource
    Transport phenomena and kinetics in an extravascular bioartificial pancreas (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 2668-2682 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A bioartificial pancreas, consisting of immobilized islets encapsulated within hollow fibers, is investigated as an alternative treatment for insulin-dependent diabetes. A mathematical model is developed to determine whether this configuration of the bioartificial pancreas can yield an insulin response to a glucose challenge with the appropriate dynamics in diabetic humans. The model consists of the 2-D mass-conservation equations for glucose and insulin within the hollow fiber and capillaries. The equations contain terms for insulin-production kinetics by porcine islets and glucose-consumption kinetics. The boundary conditions account for transport resistances of the fiber membrane, the tissue surrounding the implant, and a thin film within the capillaries. The equations are coupled to a pharmacokinetic model of the circulatory system. The calculations show that an optimized design with this configuration will be feasible for human use and requires a total volume of 4.6 mL to reach the target insulin concentration in the bloodstream following a glucose challenge. The parameters and processes controlling the system performance are discussed.
    Additional Material: 13 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420928
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  • 99
    Electronic Resource
    Electronic Resource
    Innovations in supercritical fluids: Science and technology. Edited by K. W. Hutchenson and N. R. Foster, ACS Symp. Ser. 608, American Chemical Society, 1995, 408 pp., $125.95 (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 2698-2699 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420933
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  • 100
    Electronic Resource
    Electronic Resource
    Lateral thermal dispersion in gas-liquid cocurrent downflow through packed beds (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 2977-2983 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690421025
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