Effect of a high-fat meal on the relative bioavailability of HMPL-689 in Chinese healthy volunteers.

Abstract

The aim of this study was to investigate the effect of a high-fat meal on the single-dose pharmacokinetics (PK) and tolerability of HMPL-689 in Chinese healthy volunteers. In this study, 34 eligible male volunteers received a single 30-mg dose of HMPL-689 capsules following an overnight fast or a high-fat breakfast prior to dosing. Blood samples were collected at the designated time points for pharmacokinetic analysis. Safety and tolerability were assessed throughout the study. Total 32 healthy male volunteers were completed in the study. The GMRs of AUC0-t , AUC0-∞ , and Cmax and their 90% CIs were 1.12 (1.09, 1.15), 1.12 (1.09, 1.15), and 0.64 (0.58, 0.70), respectively, in healthy male subjects after oral administration of HMPL-689 following intake of a high-fat diet versus under fasting state. The 90% CI of Cmax GMR fell outside the acceptable equivalent range (0.8-1.25). In addition, the median Tmax of HMPL-689 was 1.0 and 4.0h under the fasting and the fed conditions. The study indicated that intake of a high-fat diet had an impact on the in vivo PK profile of HMPL-689 in healthy Chinese male subjects, which could obviously reduce the oral absorption rate of HMPL-689 and had little effect on the extent of oral absorption (AUC).