Bioequivalence of the Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate Single Tablet Regimen
A Mathias*, M Menning, L Wiser, X Wei, A Dave, S Chuck and BP Kearney
Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA
- *Corresponding Author:
- Anita Mathias
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404, USA
E-mail: [email protected]
Received Date: September 10, 2012; Accepted Date: September 20, 2012; Published Date: September 25, 2012
Citation: Mathias A, Menning M, Wiser L, Wei X, Dave A, et al. (2012) Bioequivalence of the Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate Single Tablet Regimen. J Bioequiv Availab 4: 100-105. doi: 10.4172/jbb.1000121
Copyright: © 2012 Mathias A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) is a next-generation, once-daily
complete antiretroviral single-tablet regimen for the treatment of HIV-1 infection in adults. This study evaluated the pharmacokinetics and bioequivalence of 2 distinct investigational coformulations of the FTC/RPV/TDF single-tablet regimen (containing emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir disoproxil fumarate 300 mg) compared with the concurrent administration of a 200-mg strength capsule of FTC, a 25-mg strength tablet of RPV, and a 300-mg strength tablet of tenofovir disoproxil fumarate in healthy subjects. Thirty-six subjects were randomized in a single-dose, open-label, 3-way crossover study design; 34 subjects completed all study treatments. Serial blood samples were obtained over 192 hours following oral administration of each treatment and pharmacokinetic parameters calculated. Formulation bioequivalence was assessed by 90% confidence intervals (CI) for the ratio of geometric least square means (GMR) for Cmax, AUClast and AUCinf for each drug of the FTC/RPV/TDF single-tablet regimen versus the individual components. Emtricitabine, rilpivirine, and tenofovir disoproxil fumarate administered under fed conditions (standardized meal of ~400 kcal) as individual drugs given concurrently or as a fixedÃ¢ÂÂdose combination tablet were generally well tolerated. Of the 2 single-tablet formulations that were tested, a single coformulation (Test Formulation 1) demonstrated bioequivalence to the reference formulation, with 90% confidence intervals for the ratio of the geometric least-squares means contained within the bounds of 80% to 125% for the AUCinf, AUC0−last, and Cmax values of emtricitabine, rilpivirine, and tenofovir, and was carried forward as the commercial formulation. This tablet is a next-generation, once-daily single-tablet antiretroviral regimen for the treatment of HIV-1
infection and offers an attractive treatment option to efavirenz-containing regimens.