Bioequivalence of Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate Single-Tablet Regimen.

Author(s): Mathias AA, Hinkle J, Menning M, Hui J, Kaul S, Kearney BP, for the Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate Single-Tablet Regimen Development Team

Affiliation(s): From *Gilead Sciences, Foster City, CA; and daggerBristol-Myers Squibb, Princeton, NJ.

Publication date & source: 2007-07-19, J Acquir Immune Defic Syndr., Publish Ahead of Print [Epub ahead of print]

Publication type:

OBJECTIVE:: Efavirenz (EFV; 600 mg), emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg) are preferred agents for treatment of HIV-1 infection in adults. This study evaluated the pharmacokinetics (PK) and bioequivalence of an investigational coformulation of EFV/FTC/TDF (test) single-tablet regimen compared with the commercially available individual dosage forms (EFV+FTC+TDF; reference treatment) in healthy subjects. METHODS:: Subjects were randomized to 1 of 2 treatment sequences (test-->reference or reference-->test) in an open-label crossover study design. Study drug was administered under fasted conditions, and serial blood samples were obtained over 504 hours after oral administration of each treatment. Formulation bioequivalence was assessed in accordance with the US Food and Drug Administration bioequivalence criteria. RESULTS:: Forty-eight subjects were enrolled, and 45 completed the study, with all study treatments being generally well tolerated. For EFV (n = 44), the geometric mean ratios (90% confidence interval [CI]) for maximum concentration (Cmax), area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC0-last), and area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf)were 99.9 (93.4 to 107), 95.7 (90.5 to 101), and 95.2 (88.9 to 102), respectively. For FTC (n = 45), the geometric mean ratios (90% CI) for Cmax, AUC0-last, and AUCinf were 88.8 (84.0 to 93.9), 98.0 (94.9 to 101), and 98.0 (94.9 to 101), respectively. For tenofovir (n = 45), the geometric mean ratios (90% CI) for Cmax,AUC0-last, and AUCinfwere 91.5 (84.6 to 98.8), 99.3 (91.0 to 108), and 100 (93.2 to 108), respectively. CONCLUSIONS:: The coformulation of EFV/FTC/TDF is bioequivalent to administration of its individual components.