W. Sorasuchart et Jw. Ayres, Preliminary bioequivalence testing of two nicardipine HCl sustained-release formulations with in vitro/in vivo correlations, EUR J DRUG, 26(1-2), 2001, pp. 1-7
Citations number
15
Categorie Soggetti
Pharmacology & Toxicology
Journal title
EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS
A new nicardipine HCl oral sustained-release dosage form was evaluated for
bioequivalence in comparison with a reference product, Cardene(R) SR. Six h
ealthy subjects, fasted overnight, were enrolled in a single-dose, open-lab
el, randomized, and two-way crossover study. Blood samples were collected o
ver a 12 hour period, and nicardipine plasma concentrations analyzed from p
lasma. Pharmacokinetic parameters, including C-max, t(max), and AUC, were o
btained from drug plasma concentration-time curves and pharmacokinetic anal
ysis conducted using WinNonlin(R). The two one-sided t-test was applied in
statistical analysis for comparison of the pharmacokinetic parameters betwe
en the two products. There was no convincing evidence that nicardipine HCl
test product and Cardene SR were bioequivalent. Amounts of nicardipine HCl
release in vivo was mathematically obtained by deconvoluting plasma concent
ration-time data after oral administration using IV bolus injection data as
a reference. Plots of percentages of drug release in vitro against those i
n vivo illustrated triphasic curves. After the in vitro time scale was corr
ected and then plotted against in vivo data, plots provided a polynomial re
lationship (R-2 of 0.9920 and 0.9954). The in vitro/in vivo correlation may
be useful in reformulating this particular test formulation to obtain a pr
oduct with an in vivo release rate identical to Cardene(R) SR.