Title: Pharmacokinetics of nifedipine sustained release tablets in
healthy subjects after a single oral administration: Bioequivalence
study and Food effects
Abstract
Aim: This study has been designed to assess the bioequivalence of the
newly developed delayed-release oral tablets (test) 30 mg nifedipine
compared to its marketed counterpart (30 mg; reference) in healthy adult
Chinese volunteers. Methods: We conducted randomized, open-label,
four-period, crossover trials, including a fasting trial and a fed
trial. The subjects were administered the test or reference products in
a 1:1 ratio at random throughout each period with 7 days washout period.
Then, in the next session, they got the alternate products. Liquid
chromatography-tandem mass spectrometry and WinNonlin software were used
to evaluate the bioequivalence of nifedipine peak blood concentration
(Cmax) and area under the concentration-time curve (AUC). Result: A
total of 46 subjects participated in the fasting trial and 48 subjects
in the postprandial trial. In both cases, the 90% CI of the geometric
mean ratios of Cmax, AUC0-t and AUC0-∞ were in the equivalence range
(80-125%). When nifedipine was given concomitantly with a high-fat
meal, tmax was approximately twofold earlier, absorption was
approximately 4.8% less, and Cmax changed little compared to fasting
conditions. In addition, no serious adverse events were observed in the
subjects. Conclusion: This study confirms the bioequivalence of the test
and reference formulations of nifedipine extended-release tablets under
fasting and postprandial conditions. Food giving leads to a much earlier
Tmax, which is different from the results of other studies. The effect
of food effect on the pharmacokinetics of nifedipine needs to be further
explored.