Examination of two sustained release nifedipine preparations in humans and in pigs

Abstract

In the present study, the ability of the pig to discriminate the in-vivo release characteristics of two 60 mg sustained release nifedipine formulations, an experimental formulation (Faulding) and Procardia XL (Pfizer), under both fasting and fed conditions was assessed. These forms had previously been evaluated in humans, where an alteration in the release profile of the experimental formulation was noted following administration with food. 12 Large White female pigs (mean weight 38 kg) were divided into two groups and each group was orally administered one of the two products under both fasting and fed conditions. The mean area under the plasma concentration-time curve was not significantly different between the formulations under both conditions. The mean maximum observed plasma concentration ( C max) was significantly higher for the experimental formulation when compared against Procardia XL under both fasting ( P<0.05) and fed ( P<0.05) conditions. Peak concentrations were achieved at approximately 6 h for the experimental formulation and 12 h for Procardia XL. The time for which the plasma concentration exceeded 75% of C max was approximately 2.5-fold greater for Procardia XL than for the experimental formulation. There were no significant food effects on the relative bioavailability nor release profiles of the two formulations. The results obtained suggest that the pig may be a useful model in differentiating the release profiles of nifedipine formulations for the fed state in humans as results were similar to the human-fed study, but dissimilar to the human-fasted study.