Bioequivalence of Different Nitrendipine Tablet Dosage Formulations

Abstract

Summary A five-way crossover study with 30 prescreened volunteers was performed to compare two dosage formulations of Miles nitrendipine tablets with corresponding Bayer A G tablet formulations. All tablet formulations were also compared with a 20 mg liquid suspension dose of nitrendipine to determine the relative bioavailability of the tablet formulations. The nitrendipine and nitrendipine metabolite data obtained from the 26 volunteers who completed the study were examined using the General Linear Models of the Statistical Analysis System statistical package. The four tablet formulations were found to be bioequivalent in the extent of their absorption, as judged by area under the curve (AUC) values calculated using either the unchanged drug or the metabolite concentrations in plasma. The AUC values were in strong agreement with the AUC values reported for other nitrendipine tablet formulations in another bioequivalence study. In both studies 20 mg was given, and the relative bioavailability of tablet formulations was ∼ 70% when compared with a 20 mg liquid suspension dose. No significant differences were observed between either one of the Miles tablets and the Bayer tablet of the same strength, with regard to maximum nitrendipine plasma concentrations (C-max). There was also no difference between corresponding Miles and Bayer formulations for C-max values determined with the metabolite data. Although none of the differences in time to peak concentrations (T-max) of nitrendipine or metabolite were found to be significant, the Bayer formulations appeared to reach peak concentrations somewhat earlier than the Miles formulations. In contrast, the suspension dose produced significantly higher C-max and AUC, and substantially shorter T-max values than any of the tablet formulations. Although this study involved administration of an acute dose to normotensive volunteers, the T-max values coincided with maximum decrease in systolic pressure, and a relationship between nitrendipine concentration and decrease in systolic pressure was observed with tablet formulations. This study also yielded additional data on terminal nitrendipine elimination half-life. Terminal elimination half-lives, ranging from 16.5 to 30.9 h, were observed using a sensitive capillary GC procedure and 14–48 h postdose mean plasma concentrations.