Influence of food on the pharmacokinetics of apricitabine, a novel deoxycytidine analogue reverse transcriptase inhibitor

Abstract

Objective: Apricitabine is a novel deoxycytidine analogue reverse transcriptase inhibitor with clinical efficacy against both wild-type and drug-resistant HIV. The objective of this study was to evaluate the influence of feeding on apricitabine absorption and plasma pharmacokinetics. Research design/methods: Twenty healthy, male, HIV-negative volunteers were recruited for this randomised, open-label, crossover study and administered 1200 mg apricitabine orally either following fasting or a high-fat meal. Multiple blood samples were collected over a time course between 0 and 36 h following dosing, and plasma apricitabine concentration was measured using liquid chromatography–tandem mass spectrometry. Main outcome measures: Pharmacokinetic parameters were calculated from the drug concentration–time data for apricitabine using noncompartmental methods. Geometric means for maximum concentration (C_max) and area under the apricitabine concentration versus time curve (AUC) for both the fasted and fed states were calculated and tested for bioequivalence at the 0.05 level by constructing the 90% confidence interval for the ratio of geometric means. Results: Apricitabine was well tolerated by all study participants. Plasma concentrations increased rapidly following oral administration, with C_max being attained within 2 – 4 h. The pharmacokinetics of apricitabine was similar between the two states: the geometric means of both C_max and AUC increased slightly between fasting and the administration of a high-fat meal, however the 90% confidence intervals around the ratio of the geometric means were within the standard bioequivalence criteria. Conclusion: Bioequivalence between the fed and fasting states was identified, indicating that a high-fat meal had no significant impact on the pharmacokinetics of single 1200 mg doses of apricitabine in healthy volunteers.

Keywords::

• apricitabine
• AVX754
• pharmacokinetics
• HIV
• food
• nucleoside reverse transcriptase inhibitor
• antiretroviral

Acknowledgement

The authors would like to thank S Rhead of Prism Ideas for his assistance in the preparation of this article.