Bioequivalence of two orally administered nicardipine products.

The relative bioavailabilities of orally administered nicardipine (Zenith Laboratories) and nicardipine (Cardene Syntex Laboratories) were compared following a single 30 mg dose under fasted conditions using a two-way crossover study with 34 healthy adult male subjects. In a separate study the effect of food on the relative bioavailabilities of these products was assessed following an identical dose by comparing the Zenith product under fasted conditions, the Zenith product under fed conditions, and the Syntex product under fed conditions using a three-way crossover study with 17 healthy adult male subjects. In the fasted study, 90% confidence intervals surrounding ratios (Zenith/Syntex) of least-squares means derived from 1n-transformed data were 0.84-1.02 for AUCt, 0.85-1.04 for AUCinfinity, and 0.86-1.05 for Cmax, clearly demonstrating bioequivalence of the two products. In the food-effect study ratios of least-squares means (Zenith under fed conditions/Zenith under fasted conditions) were 0.62 for AUCt, 0.65 for AUCinfinity, and 0.40 for Cmax, with tmax delayed from 0.906 +/- 0.337 h (Zenith under fasted conditions) to 2.33 +/- 0.717 h (Zenith under fed conditions) and 2.84 +/- 0.834 h (Syntex under fed conditions). Findings indicate that the presence of food in the gastrointestinal tract reduces the bioavailability of orally administered nicardipine. However, ratios under fed conditions (Zenith/Syntex) were very close to unity for each metric, suggesting that the observed food effect is independent of the product formulation. Findings further suggested that food effects on conventional pharmacokinetic metrics might be attributed to alteration of extent, rather than rate, of gastrointestinal absorption. Finally, these results question the applicability of the peak plasma concentration (Cmax) as an index of absorption rate in nicardipine studies.

RCT Entities:   Population Interventions Outcomes