Comparison of the pharmacokinetics of apricitabine in the presence and absence of ritonavir-boosted tipranavir: a phase I, open-label, controlled, single-centre study.

Background And Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.