Presentaciones en Congresos

Poster's abstract Comparative pharmacokinetics of two different formulations of efavirenz By: I Ferrari1, E B Mahler1, A M Iglesias1,  C Giannone2, D Fridman3, J L Serrano3, M Ortiz3,  E Zini4, J Lazovski31Laboratory of Bioequivalence and Molecular Biology- University CAECE, Buenos Aires, Argentina; 2Biostatistics & CRO, Buenos Aires, Argentina; 3Clinical Pharmacology Unit-FUNCEI-La Sagrada Familia, Buenos Aires, Argentina; 4Richmond Laboratories, Buenos Aires, Argentina Background: The use of generic drugs assumes importance given the increasing availability of antiretroviral therapy in developing countries. Unless manufacture compliance with the WHO standards is followed, therapeutic failure and development of drug resistance may be the outcome following use of poor-quality generic antiretroviral drugs. Up to date, only very few studies have compared the pharmacokinetics or bioequivalence of generic HIV drugs against their brand-name counterparts in Argentina. The purpose of this study was to determine the pharmacokinetics and comparative bioavailability of a non-nucleoside reverse transcriptase inhibitor (NNRTI), efavirenz, manufactured by a local drug company (T - Virorrever®, Richmond Laboratories) against the innovator pharmaceutical product (R - Stocrim™ , Merck). Methods: Pharmacokinetics (PK) and comparative bioavailability of efavirenz were investigated in 18 healthy volunteers by means of a randomized two-way crossover design. After a single oral dose of 200mg efavirenz tablets, the concentration of efavirenz in plasma was determined by a modified high performance liquid chromatographic (HPLC) method with UV detection. Results: Intra-day and inter-day coefficients of variation (CV) were within 10%. The detection limit was 50ng/ml for plasma samples. Various pharmacokinetic parameters including AUC 0→00, AUC 0→144h, Cmax, Tmax and T1/2 were determined from plasma concentrations of both formulations. Statistical modules (ANOVA and 90% confidence intervals) were used to assess bioequivalence. Geometric averages (antilogarithmic) and 90% confidence intervals for AUC 0→00, AUC 0→144h and Cmax were 0.9890 (0.8010-1.2210), 1.0014 (0.8653-1.1589) and 0.9348 (0.8196-1.0661) respectively, satisfying the 80-125% bioequivalence range accepted by the US Food and Drug Administration (FDA), the European Agency for the Evaluation of Medicinal Products (EMEA) and the World Health Organization (WHO) guidances. Conclusions: Bioequivalence between the test and reference formulation can be concluded.