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


CONCLUSIONS
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.
Cox
Susan
S
Avexa Ltd, Melbourne, Victoria, Australia. scox@avexa.com.au
Southby
Justine
J
Linet
Otto
O
Tackwell
Karie
K
Borin
Marie
M
Perry
Kim
K
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004347:Drug Interactions; D006801:Humans; D008297:Male; D011725:Pyridines / Q000494:pharmacology*; D011753:Pyrones / Q000494:pharmacology*; D013449:Sulfonamides
D019380:Anti-HIV Agents; D011725:Pyridines; D011753:Pyrones; D013449:Sulfonamides; D003841:Deoxycytidine; C508042:apricitabine; C107201:tipranavir