Evaluation of the Effects of Apatinib on the Pharmacokinetics of Venlafaxine and O‐desmethylvenlafaxine in SD Male Rats by UPLC–MS/MS

• Published in: Basic & clinical pharmacology & toxicology Vol. 123; no. 6; pp. 721 - 726
• Main Authors: Bao, Su‐su, Wen, Jian, Lin, Qian‐meng, Li, Ying‐hui, Huang, Yang‐ge, Zhou, Hong‐yu, Hu, Guo‐xin
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-12-2018
• Subjects: Animals; Chromatography, High Pressure Liquid; Desvenlafaxine Succinate - blood; Desvenlafaxine Succinate - pharmacokinetics; Drug Interactions; Humans; Inhibitory Concentration 50; Liver; Male; Mass Spectrometry; Microsomes; Microsomes, Liver - drug effects; Pharmacokinetics; Pharmacology; Protein Kinase Inhibitors - pharmacology; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Rodents; Venlafaxine; Venlafaxine Hydrochloride - blood; Venlafaxine Hydrochloride - pharmacokinetics
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/bcpt.13081

The objective of this study was to evaluate the effect of apatinib on the pharmacokinetics of venlafaxine and O‐desmethylvenlafaxine in SD rats and the inhibitory effects of apatinib on venlafaxine in rat and human liver microsomes. Twenty‐one SD male rats were randomly divided into three groups (n = 7): group A (multiple dose of 40 mg/kg apatinib for 7 days), group B (single dose of 40 mg/kg apatinib) and group C (the control group). All samples were measured by UPLC‐MS/MS. The results indicated that a single dose of apatinib increased the AUC(0‐t), AUC(0‐∞) and Cmax of both venlafaxine and O‐desmethylvenlafaxine significantly, while Vz/F and CLz/F were decreased. As for group A, only AUC(0‐t) and CLz/F of venlafaxine were changed, while no parameters of O‐desmethylvenlafaxine were altered. In addition, apatinib was determined to be a mixed inhibitor of venlafaxine.