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

What is already known about this subject • Tenofovir disoproxil fumarate and some of the HIV protease inhibitors show drug–drug interactions that cannot be predicted based on their metabolic profiles. • Tenofovir disoproxil fumarate and HIV protease inhibitors are often combined as part of antiretroviral therapy. What this study adds • TMC114 (darunavir) is the latest HIV protease inhibitor approved by the US Food and Drug Administration and is used in combination with low‐dose ritonavir. • This study shows for the first time the extent of the drug–drug interaction between tenofovir disoproxil fumarate and TMC114 combined with low‐dose ritonavir and compares the interaction observed with other HIV protease inhibitors. 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 ( C min and C max ), and area under the curve (AUC 24 h ) increased by 37%, 24% and 22%, respectively. When TDF and ritonavir were coadministered, TMC114 plasma C min , C max and AUC 12 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.