Pharmacokinetic interaction between TMC114/ritonavir and tenofovir disoproxil fumarate in healthy volunteers

Abstract

Aim: TMC114 is a new HIV protease inhibitor, used in combination with low-dose ritonavir (TMC114/r) as a pharmacokinetic enhancer. Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor. Both antiretrovirals show activity against wild-type and resistant HIV. An open-label crossover study was conducted in HIV - healthy volunteers to investigate the potential for a pharmacokinetic interaction between TMC114/r and tenofovir. Methods: Two groups, each of six volunteers, were evaluated in two consecutive sessions. In session 1, volunteers received TMC114/r (300/100 mg bid) for 7 days, followed by a wash-out period of at least 6 days. In session 2, volunteers received TMC114/r (300/100 mg bid) plus TDF (300 mg qd). Results: When TMC114/r and TDF were coadministered, tenofovir plasma concentrations (Cmin and Cmax), and area under the curve (AUC24 h) increased by 37%, 24% and 22%, respectively. When TDF and ritonavir were coadministered, TMC114 plasma Cmin, Cmax and AUC12 h increased by 24%, 16% and 21%, respectively. There were no changes in the urinary excretion of unchanged tenofovir or TMC114 during coadministration. Administration of TMC114/r in HIV- healthy volunteers with or without TDF was well tolerated. Conclusions: The interaction between TMC114/r and tenofovir is not clinically relevant and no dose adjustments are required when these drugs are coadministered. © 2007 The Authors.