BIOEQUIVALENCE OF 2 ORALLY-ADMINISTERED NICARDIPINE PRODUCTS

The relative bioavailabilities of orally administered nicardipine (Zen ith Laboratories) and nicardipine (Cardene(R) Syntex Laboratories) wer e compared following a single 30 mg dose under fasted conditions using a two-way crossover study with 34 healthy adult male subjects. In a s eparate study the effect of food on the relative bioavailabilities of these products was assessed following an identical dose by comparing t he Zenith product under fasted conditions, the Zenith product under fe d conditions, and the Syntex product under fed conditions using a thre e-way crossover study with 17 healthy adult male subjects. In the fast ed study, 90% confidence intervals surrounding ratios (Zenith/Syntex) of least-squares means derived from In-transformed data were 0.84-1.02 for AUC(t), 0.85-1.04 for AUC(infinity), and 0.86-1.05 for C-max, cle arly demonstrating bioequivalence of the two products. In the food-eff ect study ratios of least-squares means (Zenith under fed conditions/Z enith under fasted conditions) were 0.62 for AUC(t), 0.65 for AUC(infi nity), and 0.40 for C-max, with t(max), delayed from 0.906+/-0.337 h ( Zenith under fasted conditions) to 2.33+/-0.717 h (Zenith under fed co nditions) and 2.84+/-0.834 h (Syntex under fed conditions). Findings i ndicate that the presence of food in the gastrointestinal tract reduce s the bioavailability of orally administered nicardipine. However, rat ios under fed conditions (Zenith/Syntex) were very close to unity for each metric, suggesting that the observed food effect is independent o f the product formulation. Findings further suggested that food effect s on conventional pharmacokinetic metrics might be attributed to alter ation of extent, rather than rate, of gastrointestinal absorption. Fin ally, these results question the applicability of the peak plasma conc entration (C-max) as an index of absorption rate in nicardipine studie s.