Comparative bioavailability of a generic capsule formulation of the reverse transcriptase inhibitor efavirenz and the innovator product

Abstract

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that has been used successfully for more than a decade to treat human immunodeficiency virus (HIV) infection. The objective of the current study was to determine the bioequivalence between a generic capsule formulation of efavirenz and the innovator product. A total of 41 healthy subjects (34 males and 8 females) received a single 200 mg oral dose of efavirenz as the generic (Ranbaxy-Efavirenz, Ranbaxy Laboratories Ltd.) and innovator (Sustiva, Bristol-Myers Squibb) capsule formulations under fasting conditions in a randomized, 2-way crossover study. Multiple blood samples were collected over 72 hours and plasma concentrations of efavirenz were assayed using an LC/MS/MS method. Pharmacokinetic (PK) parameters were calculated using non-compartmental methods. Plasma concentrations of efavirenz peaked within 2.5 hours and then declined in a multi-exponential manner for both formulations. At 72 hours post dose, all plasma concentrations of efavirenz were above the LOQ of the assay (10 ng/ml). Mean area under the curve from 0 - 72 hours (AUC0-72) and maximum plasma concentrations (Cmax) of efavirenz for the generic capsule formulation were 22,840 ng x h/ml and 1,199 ng/ml, respectively. Ratios and 90% confidence intervals of PK parameters between the two formulations were within 80.0 - 125.0%, suggesting that the two capsule formulations resulted in similar rate and extent of bioavailability under fasting conditions. Adverse events were similar in nature and frequency for the two formulations. Based on the above results, the generic capsule formulation of efavirenz developed by Ranbaxy should be as effective as the innovator product.