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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 38 (1982), S. 814-814 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Following surgical construction of a chronic end-to-side portacaval shunt, rats consumed more 6% ethanol than their controls in a schedule-induced polydipsia paradigm during the baseline condition and during intermittent food delivery. Blood enthanol was higher in rats with portacaval shunts than in controls following the final test session.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 14 (1978), S. 293-299 
    ISSN: 1432-1041
    Keywords: Breath analysis ; 14CO2 exhalation ; drug metabolism ; glycodiazine ; liquid chromatography ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Exhalation of14CO2 in breath has been used to assess the rate of hepatic demethylation of (14C-dimethyl)aminopyrine, but due to the complexity of aminopyrine metabolism the pharmacokinetics of the procedure are insufficiently understood. Therefore, studies were performed in five individuals after oral administration of (14C-methoxy)glycodiazine, a model substance with relatively simple kinetic properties. Plasma concentrations of the drug and urinary output of its metabolites measured by high pressure liquid chromatography were analysed by a two-compartment open model. The terminal disappearance of14CO2 from breath was practically identical with the terminal disappearance of glycodiazine from plasma, which could be correlated with the plasma clearance of free glycodiazine. The mean transit time of14C-atoms from plasma to breath was 3 h. These results contribute to the pharmacokinetic basis for use of14C-demethylation breath tests. In particular, they are consistent with the hypothesis that14CO2-breath analysis may be used to assess certain pharmacokinetic parameters of appropriately labelled test compounds. These parameters may not necessarily be a direct reflection of the rate of demethylation.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 17 (1980), S. 375-378 
    ISSN: 1432-1041
    Keywords: mebendazole ; echinococcosis ; bioavailability ; absorption ; concomitant eating ; plasma level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary High oral doses of mebendazole are used experimentally for the treatment of human alveolar and cystic echinococcosis. In order to assess bioavailability of this drug 1.5 g doses were given to 3 volunteers. Measurable plasma concentrations of 17 to 134 nmol/l were found only if mebendazole was given together with a fatty meal. In a patient with cholestasis plasma concentrations were higher than in the 3 normal subjects. In patients on long term treatment the increase in plasma concentration after administration of a 1 g dose varied between 0 and 500 nmol/l. It is concluded that systemic availability of mebendazole is enhanced by concomitant food intake. In view of the large intra- and interindividual variation in plasma concentration, monitoring plasma levels during long term therapy appears advisable.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 21 (1981), S. 53-59 
    ISSN: 1432-1041
    Keywords: caffeine ; breath test ; phenobarbital ; methylcholanthrene ; cirrhosis ; smoking ; cytochrome P-448 ; demethylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary [1-Methyl-14C], [3-Methyl-14C] and [7-Methyl-14C] caffeine were used to investigate demethylation in control rats, and in rats pretreated with phenobarbital or 3-methylcholanthrene, by a14CO2-exhalation test. Compared to controls, pretreatment with phenobarbital did not enhance demethylation of any of the labelled caffeines. In contrast, induction by 3-methylcholanthrene, presumably of cytochrome P-448, resulted in highly significant increases in peak14CO2 exhalation rates,14CO2 disappearance constants and areas under the exhalation rate — time curves. Based on these results, [7-methyl-14C] and [3-methyl-14C] caffeine were chosen for assessing the feasibility of a caffeine breath test in man, using 5 normal volunteers and 2 patients with compensated liver cirrhosis.14CO2 exhalation curves in cirrhotics were clearly different from those in normal volunteers, being characterised by a slower rise and a lower specific activity of exhaled14CO2. Since the variability of the levels of the specific activity in subjects with normal livers suggested the influence of extraneous factors, a second group of normal volunteers, smokers and nonsmokers, was investigated. With either labels, the average14CO2 exhalation rate was doubled in smokers. From these studies in rats and preliminary results in man it is concluded that specifically labelled caffeine is a suitable and promising substrate for studying demethylation by breath analysis. Presumably, caffeine represents a safe and sensitive indicator of the activity of the cytochrome P-448 system.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 24 (1983), S. 485-494 
    ISSN: 1432-1041
    Keywords: amiodarone ; pharmacokinetics ; therapeutic serum level ; thyroid function ; antiarrhythmic therapy ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 17 patients on long term therapy with amiodarone, serum drug levels measured by HPLC were related to pharmacological effects. At steady state, serum levels were directly proportional to the dose, 5 mg/kg per day leading to an average serum level of approximately 2.5 µmol/l. The non-amiodarone level of iodine averaged 4-times higher than the level of amiodarone iodine. The elimination half-life of amiodarone ranged from 21 to 78 days, and of non-amiodarone iodine from 24 to 160 days. Control of arrhythmias was satisfactory in all 12 evaluable patients, when the serum amiodarone level exceeded 1.5 µmol/l. Deterioration of vision and polyserositis occurred only at amiodarone levels above 4 µmol/l. Tentatively, a therapeutic range of 1.5 to 4 µmol/l is proposed. In contrast, thyroid dysfunction was observed at any amiodarone level. In view of the narrow therapeutic window, therapy with amiodarone may be optimized by monitoring its serum level and in addition, thyroid function should be regularly checked.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 31 (1986), S. 443-448 
    ISSN: 1432-1041
    Keywords: echinococcosis ; mebendazole ; long-term course ; plasma levels ; drug interactions ; cimetidine ; ursodeoxycholic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma mebendazole levels were analysed retrospectively in patients treated for inoperable infections withEchinococcus multilocularis orgranulosus. In 10 patients receiving mebendazole at 4 dose levels there was no relation between dose and plasma concentration. In 17 patients followed on the same dose for more than 18 months, the plasma levels varied with individual coefficients of variation ranging from 27 to 72%. The data reveal the limitations of single measurements of plasma mebendazole and emphasize the need for repeated monitoring. Coadministration of phenytoin and carbamazepine seemed to lower plasma levels, presumably as a result of enzyme induction. It was not possible appreciably to raise the mebendazole concentrations by inhibition of drug metabolizing enzymes with cimetidine.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 30 (1986), S. 407-416 
    ISSN: 1432-1041
    Keywords: malotilate ; cirrhosis ; bioavailability ; liver fibrosis ; metabolite kinetics ; pharmacokinetics ; portal-systemic shunting ; urinary metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Malotilate, a sulphur-containing compound with antifibrotic and hepatoprotective properties in several animal models, has been investigated in cirrhotic patients. Nine patients with cirrhosis of various aetiologies and severity, and 4 healthy volunteers, participated in a pharmacokinetic study. After a single dose of 500 mg malotilate p.o. peak malotilate plasma concentration measured by GC-MS was 35 times higher in patients (median 0.70 µg/ml) than in controls (median 0.019 µg/ml). The median apparent oral clearance was approximately 50 times lower in cirrhotics (median 2.2l/min) than in healthy volunteers (118l/min). The apparent oral clearance was significantly correlated with indicators of portalsystemic shunting, such as the 2-h postprandial serum bile acids and the bioavailability of oral nitroglycerine. Urinary output of the glucuronidated metabolite-(M3), measured by HPLC, was normal in patients, whereas recovery of metabolite-M6 (resulting from ring opening and loss of sulphur) was reduced. Six patients in an open 6-month trial received malotilate 200 mg t.i.d. for 2 months and 400 mg t.i.d. for 4 months. The thrombocyte count increased and serum ferritin level fell in all patients, and serum cholinesterase rose and IgA decreased in 5 of 6. The other indicators of liver function did not show a significant change. Dry skin was the only possible adverse effect. It is concluded that first-pass elimination of malotilate is dramatically reduced in cirrhotics, and that a smaller amount of the drug reaches the liver in such patients. Malotilate was well tolerated, even in patients with advanced disease.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 181-187 
    ISSN: 1432-1041
    Keywords: midazolam ; triazolam ; dose equivalence ; flicker sensitivity ; reaction time ; digit symbol substitution test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacodynamic potency of oral midazolam, a new ultrashort-acting hypnotic benzodiazepine, has been evaluated relative to a standard dose of triazolam, a well established oral benzodiazepine with a similar pharmacological profile. In a balanced design, double-blind cross-over study 6 healthy volunteers received 3.75, 7.5, and 15 mg midazolam and 0.25 mg triazolam orally, at 8 a.m., at weekly intervals. Drug effects were repeatedly measured over 8 h by a new psychometric method, the threshold amplitude for perception of flickering light (TPF) assessed at 5 and 30 Hz. Auditory reaction time, digit-symbol substitution test (DSST), and self-rating by subjects served as reference standards. Median midazolam doses equivalent to 0.25 mg triazolam, interpolated on dose-response curves for peak effects, were 5.2 mg (TPF 30 Hz), 6.4 mg (TPF 5 Hz), 6.5 mg (DSST), and 7.4 mg (reaction time), respectively. Alternative methods of data analysis gave similar results. Introduction of TPF as a highly reproducible and sensitive measure of the effect of benzodiazepines on the CNS offers new opportunities to compare the relative potencies of different benzodiazepines in man. Since clinical experience has shown 0.25 mg triazolam to be safe and effective, it is concluded that the corresponding single oral dose of midazolam is between 5 and 8 mg.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 39 (1990), S. 245-251 
    ISSN: 1432-1041
    Keywords: Paracetamol ; drug conjugation ; renal elimination ; glucuronidation ; sulphation ; metabolic capacity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Factors which might affect paracetamol disposition have been studied in a heterogenous group of patients in need of mild analgesia in an intensive care unit. Following oral administration of 1 g of paracetamol, plasma and urinary concentrations of the parent compound and metabolites were assessed by HPLC. The renal clearance of paracetamol was significantly correlated with urine flow (r=0.84) and creatinine clearance (r=0.77), but not with urine pH. Metabolite output was diminished in patients with reduced renal function. Despite the heterogeneity of patients and the diversity of drug treatment, the urine to plasma paracetamol concentration ratio appeared remarkably constant in patients with normal renal function (9.8±2.7). It is concluded that the metabolite to paracetamol ratio may only be regarded as a measure of the drug metabolizing capacity in subjects with normal renal function, if factors influencing urine volume and paracetamol absorption are standardized.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 38 (1990), S. 87-89 
    ISSN: 1432-1041
    Keywords: Aminopyrine breath test ; Sorbitol clearance ; interaction ; liver disease ; Drug metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of sorbitol on the aminopyrine breath test was investigated in 13 patients with various liver diseases given a bolus dose of sorbitol 20 mg · kg−1 i. v. 30 min after 14C-aminopyrine and 13 patients without the sorbitol bolus who also underwent an aminopyrine breath test. The time course of 14CO2 exhalation after the bolus of sorbitol did not differ from that in the control group.
    Type of Medium: Electronic Resource
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