The bioavailability of oral nifedipine formulations: A statistical and simulation approach
โ Scribed by F. Kozjek; S. Primozic; A. Mrhar; R. Karba; K. D. Raemsch; A. Janezic
- Publisher
- John Wiley and Sons
- Year
- 1987
- Tongue
- English
- Weight
- 596 KB
- Volume
- 8
- Category
- Article
- ISSN
- 0142-2782
No coin nor oath required. For personal study only.
โฆ Synopsis
The bioequivalence of three oral forms of nifedipine was assessed in a triple crossover study on 12 healthy volunteers. Single 10 mg dose was given and ten blood samples were drawn during the first 8 h after administration. Highly sensitive gas chromatographic method was used for the nifedipine assay. Pharmacokinetic parameters which describe bioavailability and general kinetic behaviour of the drug (AUC, C,,,, fmax, beta, MRT) were calculated from individual plasma profiles. They were subjected to statistical analysis (paired t-test, Hauck's inverted t-test, and Westlake's method of confidence intervals). Analogue-hybrid simulation and identification was used to generate plasma profiles of nifedipine after single and multiple dosing. Averaged plasma concentrations were used for this purpose. The three formulations studied were bioequivalent in terms of the rate of absorption. The simulation proved to be an efficient tool to substitute in vivo multiple dosing studies for assessment of bioavailability. The specific statistical methods should be preferred in bioequivalence data evaluation due to their greater power and inclusion of extraneous bioequivalence limits interval. Despite the differences among the formulations studied, each one of them should be viewed according to its intended clinical use.
๐ SIMILAR VOLUMES
Previous studies with rats indicate that nifedipine undergoes both hepatic and extrahepatic presystemic metabolism after peroral (po) administration, and that its bioavailability is increased and absorption delayed by concomitant administration of grapefruit juice concentrate (GJC). Hence, the effec