摘要:

AbstractA new sustained release dosage form of valproic acid (VPA) was developed. The new sustained release dosage form was administered (twice, with and without food) to five dogs in comparison to a standard tablet (Depakine, Labaz) and an i.v. preparation of the drug. Drug level monitoring in the plasma was performed by a GLC assay. Results indicate that the sustained release formulation exhibited a more prolonged and uniform absorption rate, yielded more sustained plasma levels after ingestion, and showed an overall bioavailability of 0·84 (95 per cent C.I. = 0·72, 0·96) relative to an equivalent dose of a conventional tabl

ISSN:0142-2782    

DOI:10.1002/bdd.2510050102

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractThe dissolution profiles of two brands of triamterene–hydrocholorthiazide (TRM–HCT) combination tablets and two brands of TRM–HCT combination capsules were studied using the USP paddle method at 100 rev min−1in acid medium (0·1N). The tablets represent two products marketed in Germany, whereas the capsules represent the approved innovator's product and an unapproved generic product. The tablets dissolved almost 100 per cent in 15 min whereas the capsules dissolved less than 25 per cent in 60 min. A pilot bioavailability study was carried out in four normal healthy male volunteers. Urine samples were collected over a 48 h period and analysed for TRM, its major metabolite TRM‐sulfate, and HCT using HPLC methods. The dissolution characteristics of TRM can be associated with the total drug excretion (absorption) of the product. On the other hand, the excretion (absorption) of HCT was independent of dissolution characteristics of the products. However, in TRM–HCT combination product, there appears to be a 50 per cent reduction in HCT excretion (absorption) when compared to the reported excretion (absorption) from a marketed single‐

ISSN:0142-2782    

DOI:10.1002/bdd.2510050103

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractGentamicin was administered s.c. to rats once daily for 7 days at 5 mg kg−1. At the end of this period renal concentrations of gentamicin declined from day 1 to day 5 post‐dosing, but showed a second peak on day 8, after which they declined again through days 16 and 22. This second peak coincided with a peak of mitotic activity in the kidney, suggesting that this organ, while recovering from gentamicin‐induced damage, passes through a temporary phase during which it has increased affinity for genta

ISSN:0142-2782    

DOI:10.1002/bdd.2510050104

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractTwo sensitive analytical procedures, a radioimmunoassay (RIA) and a mass fragmentographic (GC–MS) method, were used to quantitate plasma trifluoperazine concentrations over 24 h in five healthy male volunteers following single 5 mg doses of two trifluoperazine tablet formulations (A and B) in a two‐way cross‐over design. Bioavailability in terms of area under the plasma concentration versus time curve to 24 h or extrapolated to infinity, maximum plasma concentration and time to maximum plasma concentration using either RIA or GC–MS was not statistically significantly different from one formulation to the other. Also, there were no statistically significant differences between GC–MS and RIA values for AUC024andCmaxfor each of the two formulations examined. However, the mean AUC024RIA/GC–MS ratios for formulations A and B were 3·1 and 3·4, respectively, while the meanCmaxRIA/GC–MS ratios were 1·7 and 2·1, respectively. These differences in AUC andCmaxare probably mainly due to the relative non‐specificity of the RIA antiserum. Thus, where GC–MS is preferred for pharmacokinetic studies, both analytical procedures can be used for comparative single‐dose bioequivalence studies of trifluoperazine. However, both the methods should be tested in patients in order to establish the suitability of one procedure over the other for the study of plasma level versus clinica

ISSN:0142-2782    

DOI:10.1002/bdd.2510050105

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

Abstract‘In vitro’ and ‘in vivo’ studies were used to determine the interaction of naproxen, an anti‐inflammatory agent, and cholestyramine, a hypocholesterolemic substance.Cholestyramine shows a marked affinity for naproxen and the intensity of this is governed by the pH values. The maximum amount of naproxen adsorbed by the resin is close to 2·2 mMg−1.The pharmacokinetics of naproxen was studied in eight healthy volunteers after concurrent oral administration in a single dose of 250 mg of naproxen and 4 g of cholestyramine. The resin causes an important delay in the incorporation of naproxen into the systemic circulation, though no significant modifications are seen to take place in any other pharmacokinetic parameters

ISSN:0142-2782    

DOI:10.1002/bdd.2510050106

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractThe influence of vitamin C on the pharmacokinetics of antipyrine was investigated in eleven elderly men aged 65–74. Antipyrine (15 mg kg−1) was administered intravenously on three separate occasions over a 7‐week period: (a) before dietary vitamin C restriction, (b) after approximately 5 weeks of dietary vitamin C restriction, and (c) after 2 weeks of vitamin C supplementation (500 mg orally twice daily). The mean plasma and leucocyte vitamin C levels (±S.D.) before vitamin C restriction were 1·26 ± 0·31 mg dl−1and 26·6 ± 6·7 μg 10−8leucocytes, respectively. These values decreased and then increased significantly following vitamin C restriction and supplementation, respectively. The mean plasma half‐life of antipyrine was 10·2h and the mean plasma clearance was 2·561h−11·73 m−2before vitamin C restriction. No significant changes in the clearance, volume of distribution, or half‐life of antipyrine occurred during the study, indicating that short‐term alterations in vitamin C intake do not affect the pharmacokinetics

ISSN:0142-2782    

DOI:10.1002/bdd.2510050107

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractUptake of chlorothiazide by red blood cells after oral drug administration was investigated. Chlorothiazide was administered to normal healthy volunteers as a solution or a tablet. Frequent blood samples were collected and analysed by a specific HPLC method. The results indicate that there is a significant uptake of chlorothiazide by red blood cells, resulting in a higher blood AUC compared to plasma AUC.

ISSN:0142-2782    

DOI:10.1002/bdd.2510050108

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractThe effects of formulation, particle size, coadministration of food, antacids, or antiulcer agents on the bioavailability of etodolac (ULTRADOL®, 1,8‐diethyl‐1,3,4,9‐tetrahydropyrano[3,4‐b]indole‐1‐acetic acid), a novel non‐steroidal anti‐inflammatory agent, have been evaluated in dogs and man. The effects of dosage regimen and/or repetitive dosing on bioavailability were also determined. In man, capsule and tablet dosage forms containing micronized etodolac were shown to have a bioavailability (AUC) equal to that of the reference etodolac solution. Etodolac from tablets and capsules was rapidly absorbed since only minor decreases inCmaxand increases intmaxwere observed compared to the etodolac solution. In a comparison of regular and micronized etodolac dosage forms, both in dogs and man, similar findings, i.e. no change in AUC but small parallel changes inCmaxandtmax, were noted. Administration of etodolac with food had no effect on etodolac bioavailability in dogs but tended to cause a delay in its absorption. Coadministration of an antacid, magaldrate, or the antiulcer agent, sucralfate, had no effect on the bioavailability of etodolac in dogs, although with the latter, a significant reduction inCmaxwas noted. In man, etodolac may be administered as a single bolus dose or in divided (b.i.d.) doses without any loss in bioavailability. With either regimen, on repeat administration for 7 days, no etodolac accumu

ISSN:0142-2782    

DOI:10.1002/bdd.2510050109

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

摘要:

AbstractSome authors have used an elimination rate constant derived from one theophylline treatment (e.g. the elixir) to apply the Wagner–Nelson method to concentration–time data from another treatment (e.g. a sustained‐release form). Since there is considerable intrasubject variation in the elimination rate constant of theophylline such a practice usually involves use of an incorrect rate constant. By means of theoretical treatment and simulations the effects of such a practice are shown and illust

ISSN:0142-2782    

DOI:10.1002/bdd.2510050110

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510050111

出版商:John Wiley&Sons, Ltd.    

年代:1984

数据来源: WILEY