Influence of verapamil on pharmacokinetics of pristimerin in rats

Abstract The aim of this study was to investigate the effects of verapamil on the pharmacokinetics of pristimerin in rats. A sensitive and reliable LC‐MS/MS method was developed and applied for the determination of pristimerin in rat plasma. The pharmacokinetics of orally administered pristimerin with and without verapamil pretreatment was investigated. The results indicated that, when the rats were pretreated with verapamil, the peak concentration of pristimerin increased from 189.13 to 277.53 ng/mL (46.7%), and the AUC 0– t increased by approximately 82.0%. Additionally, the effects of verapamil on the absorption and metabolic stability of pristimerin were investigated using the Caco‐2 cell transwell model and rat liver microsomes. A markedly higher transport of pristimerin across the Caco‐2 cells was observed in the basolateral‐to‐apical direction and was abrogated in the presence of the P‐gp inhibitor, verapamil. These results indicated that P‐gp might be involved in the absorption of pristimerin. Of note, the metabolic half‐life of pristimerin was prolonged by the pretreatment with verapamil. In conclusion, verapamil could affect the pharmacokinetics of pristimerin, and it might work through increasing the absorption of pristimerin by inhibiting P‐gp, or through slowing down the metabolism of pristimerin in the rat liver. Copyright © 2015 John Wiley & Sons, Ltd.