Fixed-dose formulation of efavirenz/tenofovir/FTC bioequivalent to separate dosing

A study by Mattias and colleagues from Gilead Sciences reported pharmacokinetic bioequivalence between the co-formulated fixed dose combination of efavirenz, tenofovir and FTC and plasma levels achieved when each drug was taken as single drug formulations.

48 HIV-negative volunteers were enrolled in a randomised cross-over study, using either test or reference formulations for one week, followed by a one week washout before switching formulations for a further week. Intensive PK was performed after each treatment.

Bioequivalence was assessed by 90% CI for the geometric least square means for Cmax AUC-t and AUC-infinity for each drug.

Comment

This is the first collaboration between two research-based pharmaceutical companies (Gilead and BMS) to produce a three-drug fixed-dose formulation. Although the project was announced by both companies in December 2004, several earlier attempts failed to produce bioequivalent results. This highlights the practical complexity of pharmacology, in an area than many people would expect to be routine and straight-forward.

Matthias A, Plummer A, Kearney B et al. Bioequivalence of the co-formulation of efavirenz/emtricitabine/tenofovir DF. 7th International Workshop on Clinical Pharmacology of HIV Therapy, 20-22 April 2006, Lisbon. Abstract 82.