Zeitschrift für Bioäquivalenz und Bioverfügbarkeit

Abstrakt

Bioequivalence and Pharmacokinetics of a Fixed-Dose Combination of Dolutegravir, Lamivudine and Tenofovir Disoproxil Fumarate in Healthy Thai Volunteers

Wiwat Supasena, Ekawan Yoosakul, Mathus Sawpitiporn, Charinthon Seeduang, Suchada Rakphung, Anas Sunhem, Mariam Duereh, Jaturavit Vattanarongkup, Vipada Khaowroongrueng, Lalinthip Saeaue, Busarat Karachot, Piengthong Narakorn, Porranee Puranajoti, Isariya Techatanawat

A regimen of dolutegravir, lamivudine and tenofovir disoproxil fumarate has been approved to treat Human Immunodeficiency Virus (HIV) infection. To enhance patient adherence and accessibility to combined antiretroviral therapy, a fixed-dose combination formulation for this regimen had been developed. A comparative randomized, single dose, two-way crossover, open-label study was conducted in 52 healthy Thai volunteers to evaluate the bioequivalence and pharmacokinetics of the fixed-dose combination compared with those of separate tablets. Blood samples were collected through 72 hours post-dose. The concentrations of dolutegravir, lamivudine and tenofovir, an active metabolite of tenofovir disoproxil fumarate in the processed plasma samples were determined using two validated LC-MS/MS methods. The primary pharmacokinetic parameters were the area under the plasma concentration-time curve (AUC_0-tlast) and the maximum concentration of drug in plasma (C_max). The results showed that the fixed-dose combination was bioequivalent to the reference products in terms of rate and extent of absorption of each drug as indicated by the 90% confidence intervals of the geometric least squares mean ratios (test/reference) for ln-transformed AUC_0-tlast and C_max, which were within the acceptance range of 80.00%-125.00%. Both products were well tolerated by the study subjects. There were no serious adverse events reported in this study. The results support the use of fixed-dose combination product as an alternative product of three separate tablets.