Comparison of the Pharmacokinetics of Apricitabine in the Presence and Absence of Ritonavir-Boosted Tipranavir: A Phase I, Open-Label, Controlled, Single-Centre Study

• Published in: Clinical drug investigation 2009-01, Vol.29 (11), p.721-728
• Main Authors: Cox, Susan, Southby, Justine, Linet, Otto, Tackwell, Karie, Borin, Marie, Perry, Kim
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anti-HIV Agents - pharmacokinetics; Area Under Curve; Clinical trials; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacokinetics; Drug Interactions; Drug therapy; Health aspects; HIV infection; Humans; Internal Medicine; Male; Management; Medicine; Medicine & Public Health; Original Research Article; Pharmacokinetics; Pharmacology/Toxicology; Pharmacotherapy; Pyridines - pharmacology; Pyrones - pharmacology; Reverse transcriptase inhibitors
• ISSN: 1173-2563; 1179-1918
• DOI: 10.2165/11319890-000000000-00000

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 ∼40% and in the apricitabine maximum plasma concentration of ∼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.