apricitabine and tipranavir

Topics: Anti-HIV Agents; Benzophenones; Cytidine Triphosphate; Darunavir; Deoxycytidine; Emtricitabine; HIV; HIV Fusion Inhibitors; HIV Reverse Transcriptase; Humans; Imidazoles; Nitriles; Protease Inhibitors; Pyridazines; Pyridines; Pyrimidines; Pyrones; Reverse Transcriptase Inhibitors; Sulfonamides; Sulfur Compounds; Zalcitabine

Apricitabine is a deoxycytidine analogue nucleoside reverse transcriptase inhibitor for the treatment of HIV infection. The aim of this phase I study was to investigate whether administration of apricitabine with the HIV protease inhibitor tipranavir (ritonavir-boosted) affects the pharmacokinetic profile of apricitabine.. This phase I study was conducted in 18 healthy adult male subjects. Subjects received a single dose of apricitabine 800 mg on the morning of day 1 followed by tipranavir 500 mg plus ritonavir 200 mg every 12 hours from day 2 to day 9 to achieve steady-state concentrations of tipranavir/ritonavir. On day 10, subjects received a single morning dose of apricitabine 800 mg and a single dose of tipranavir 500 mg plus ritonavir 200 mg. Following dosing on days 1, 9 and 10, pharmacokinetic sampling was undertaken over 12 hours post-dosing to determine the plasma concentrations of apricitabine and tipranavir.. The administration of a single dose of apricitabine 800 mg in the presence of steady-state tipranavir/ritonavir concentrations resulted in an increase in the apricitabine area under the plasma concentration-time curve of approximately 40% and in the apricitabine maximum plasma concentration of approximately 25% relative to apricitabine 800 mg administered alone. Apricitabine was well tolerated when administered with tipranavir/ritonavir.. A moderate increase in apricitabine exposure was seen after co-administration with ritonavir-boosted tipranavir but this increase was not of clinical significance. No adjustment of apricitabine dosing is required when administered with ritonavir-boosted tipranavir.

Topics: Adolescent; Adult; Anti-HIV Agents; Area Under Curve; Deoxycytidine; Drug Interactions; Humans; Male; Pyridines; Pyrones; Sulfonamides