ISSN:0142-2782    

DOI:10.1002/bdd.2510070102

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractA group of 15 rats received two intravenous bolus doses of antipyrine (15 mg/kg) separated by a 57 hour infusion (with bolus dose) of phenobarbital. Phenobarbital bolus doses and infusion rates were based on a preliminary pharmacokinetic study (7 rats) and were varied to achieve a broad range of steady state levels. Antipyrine and phenobarbital blood levels were measured by high pressure liquid chromatography. Antipyrine kinetics obeyed first order monoexponential decay, and the parameters (clearance, volume, half‐life) were determined. Antipyrine clearance increased in all animals during phenobarbital infusions with a per cent increase ranging between 54·6 and 269 per cent. However, no significant correlation was found between the per cent increase in antipyrine clearance and phenobarbital concentration (r= 0·19). The volume of distribution of antipyrine increased in 14 of 15 animals with increases ranging between 7·7 and 45·8 per

ISSN:0142-2782    

DOI:10.1002/bdd.2510070103

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractAcetylsalicylic acid (ASA) was administered orally as a single dose to 7 healthy male volunteers as plain or enteric‐coated (EntrophenR) tablets using a crossover design. Blood and urine samples were collected and analysed for ASA metabolites by high performance liquid chromatography. Labile and stable glucuronide conjugates of salicylic acid (SA) were measured in urine after differential hydrolysis with glucuronidase. Plasma kinetic parameters for the ASA metabolites SA and salicyluric acid were not different for the 2 formulations, apart from the delayed appearance after the enteric‐coated tablets. Total urinary recovery, and recovery of salicyluric acid and the two SA glucuronides were not different, thus confirming the equivalent bioavailability and metabolite profile of the 2 ASA formulati

ISSN:0142-2782    

DOI:10.1002/bdd.2510070104

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractA pilot bioavailability study was carried out to evaluate the drug interaction and influence of dioctyl sodium sulfosuccinate (DS) on the absorption/bioavailability of tetracycline. Three tetracycline products—a fast dissolving capsule, a slow dissolving capsule and a suspension, were used in the study. DS was administered (a) 30 minutes before tetracycline administration; and (b) on −3, −2 and −1 day in the evening before tetracyline administration. Frequent urine samples were collected up to 48 hours and analyzed by a microbiological method. Although not statistically significant in this small study, the results suggest that there is a reduction in tetracycline bioavailability due to DS. The indiscriminate use of surface active agents to increase the dissolution rate of solid oral dosage forms in the belief that the resulting increased dissolution improves product bioavailability must be que

ISSN:0142-2782    

DOI:10.1002/bdd.2510070105

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractThe bioequivalence of two new investigational 160 mg tablets, one containing the regular form and the other a micronized form of megestrol acetate, was determined relative to a commercially available 40 mg tablet (Megace®). The tablets were administered to 24 male subjects in a three‐way cross‐over study, balanced for sequence, with a week between administrations. The 40 mg tablets were administered q.i.d. at 08.00, 12.00, 18.00 and 22.00 h, while the 160 mg tablets were administered once at 08.00 h. Plasma samples were collected at appropriate times out to 96 h after administration and were analysed for megestrol acetate with a validated high performance liquid chromatographic procedure. Based on the times to maximum plasma concentrations (2·5 to 2·8 h), the absorption rate constant was the same for each of the tablets. Relative to the 40 mg q.i.d. dose, the 160 mg regular and the 160 mg micronized tablets had mean relative bioavailabilities of 97 per cent and 118 per cent, respec

ISSN:0142-2782    

DOI:10.1002/bdd.2510070106

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractThe pharmacokinetics of prenalterol in healthy young volunteers after i.v. and oral dosing has been studied. There is evidence of non‐linearity following the i.v. dosing. Evidence of dose‐dependent pharmacokinetics following i.v. dosing has been obtained. The sustained‐release formulation is very effective: almost 12 h were needed to achieve 50 per cent of the tota

ISSN:0142-2782    

DOI:10.1002/bdd.2510070107

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractThe pharmacokinetics of oral midazolam (Dormicum®, 15 mg) and loprazolam (Dormonoct®, 1 mg) were studied in eight healthy young volunteers in a cross‐over design. Plasma concentrations of midazolam were measured with a gas chromatographic method and loprazolam concentrations were determined by a radio‐receptor technique. Absorption of midazolam proceeded very rapidly (mediantmax= 0.4 h) and a rapid onset of sedative action was observed. Loprazolam absorption was relatively slow (mediantmax= 3 h) and its absorption profile was often irregular. Most subjects fell asleep before peak concentrations were reached. Median peak concentrations were 94 ng ml−1and 3·1 ng ml−1for midazolam and loprozolam, respectively. The median elimination half‐life of midazolam was 1·8 h and that of loprazolam 15 h. It is possible that the elimination half‐life of loprazolam as determined by radioreceptor assay is determined by active metabolites rather than by loprazolam itself. Midazolam elimination half‐life was the same when determined by radioreceptor assay or by GLC. There was no significant correlation between the half‐liv

ISSN:0142-2782    

DOI:10.1002/bdd.2510070108

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractIn order to examine a potential interaction between isoxicam and propranolol, single 200 mg doses of isoxicam were administered to ten healthy male volunteers before and during treatment with propranolol, gradually attaining a dose of 80 mg t.i.d. for 11 days. The pharmacokinetic profiles of the isoxicam plasma concentration/time data obtained over 96 h following the doses of isoxicam before and during propranolol administration were compared. No significant change was found in any of the pharmacokinetic parameters determined. These results suggest that propranolol has no effect on the metabolic disposition of isoxicam.

ISSN:0142-2782    

DOI:10.1002/bdd.2510070109

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractA new gas chromatographic method was developed for the quantification of levamisole in human plasma and urine, using a nitrogen–phosphorus flame ionization detector. The adsorption of the drug onto glass was prevented by treating the glassware with a siliconizing agent. The sensitivity of the assay was 10 ng ml−1and as low as 2 ng ml−1can be detected in plasma.The urinary metabolitep‐hydroxylevamisole was analysed by high performance liquid chromatography with ultraviolet detection. The sensitivity of this assay was 0·50 μg ml−1.Plasma and urinary concentrations of levamisole were determined in 10 healthy volunteers including seven men and three women following the administration of a single 150 mg dose of levamisole. Levamisole was rapidly absorbed (tmax1·5 h), giving a peak plasma concentration of 716·7 ± 217·5 ng ml−1. The plasma elimination half‐life of levamisole was 5·6 ± 2·5 h. Only 3·2 ± 2·9 per cent of the oral dose was recovered as unchanged drug in the urine, suggesting the importance of clearance of levamisole by routes other than the kidney, and most probably by hepatic metabolism.The urinary concentrations ofp‐hydroxylevamisole were determined before and after hydrolysis of the urine samples with β‐glucuronidase, and the level of conjugation of the metabolite with glucuronic acid was then estimated. Cumulative recovery of the metabolite accounted for 1·6 ± 1·1 per cent and 12·4 ± 5.5 per cent of the oral dose of levamisole before and after hydrolysis, respectively, indicating thatp‐hydroxylation is a relatively important route of metabolism of levamisole, and that thep‐hydroxylated metabolite is excreted mainly in conjugation with glucuronic acid.Except for the absorption rate of levamisole which is approximately twice as rapid in women as in men, there is no marked difference in the pharmacokinetics of l

ISSN:0142-2782    

DOI:10.1002/bdd.2510070110

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractThree simple linear and three simple non‐linear pharmacokinetic models are presented which incorporate the reversible metabolism that occurs between prednisone and prednisolone. Under steady‐state conditions it is possible to not only distinguish between the linear and non‐linear models but also to determine which particular model of each group applies to a given set of data. While the non‐linear conversion of prednisolone to prednisone is important in explaining the pharmacokinetics of prednisone in all three non‐linear models, the same is not true for pre

ISSN:0142-2782    

DOI:10.1002/bdd.2510070111

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY