Effects of verapamil on pharmacokinetics of Y101 in vivo in rats
10.3969/j.issn.1001-1978.2021.08.016
- Author:
Ai-Jiel ZHANG
1
;
Fan-Long YANG
1
;
Shi-Qi DONG
1
;
Jian-Feng LIU
1
;
Hui-Rong FAN
1
;
Shi-Qi DONG
2
;
Jian-Feng LIU
2
;
Hui-Rong FAN
2
;
Lu ZHAO
3
;
Cai LI
3
Author Information
1. Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College
2. Key Laboratory of Radio-phannacokinetics of Innovative Drug, Chinese Academy of Medical Sciences,
3. Tianjin University of Traditional Chinese Medicine
- Publication Type:Journal Article
- Keywords:
LC-MS/MS;
metabolites;
P-gp;
pharma¬cokinetics;
verapamil;
Y101
- From:
Chinese Pharmacological Bulletin
2021;37(8):1122-1127
- CountryChina
- Language:Chinese
-
Abstract:
Aim To develop a liquid chromatography electrospray-ionization tandem mass spectrometry (LC- MS/MS) method for simultaneous determination of bentysrepinine (Y101) and its metabolites M8 and M9 in rat plasma and to investigate the effect of verapamil, an inhibitor of P-glycoprotein (P-gp) , on the pharma¬cokinetics of Y101, a substrate of P-gp, in rats. Methods SD rats were divided randomly into two groups; ( 1) Y101 only as a control group, received an oral dose of 60 mg • kg"1 Y101; (2) Verapamil plus Y101 as an experimental group, received an oral dose of 60 mg • kg"1 Y101 in combination of 25 mg • kg"1 verapamil. The plasma concentrations of Y101 and its metabolites were determined by LC-MS/MS method af¬ter intragastric administration, and the pharmacokinetic parameters were calculated using non-compartmental a- nalysis. Results We successfully developed and fully validated a LC-MS/MS method, which simultaneously determined the concentration of Y101 and its metabo¬lites in rat plasma. The AUC0_t for Y101 and M9 in experimental group increased to 1.71-fold and 1.58- fold in comparison of control group. At the same time, the plasma clearance of Y101 and M9 decreased to 60% of control. However, we did not find any differ¬ence in AUC0_l and plasma clearance for M8 between two groups. Conclusions The validated LC-MS/MS method is sensitive and rapid for the determination of Y101 and its metabolites in rat plasma and was suc¬cessfully applied to the pharmacokinetic study in rats. Verapamil, a P-gp inhibitor, significantly increases the exposure of Y101 and its metabolites in vivo, indicating the adjustment of Y101 dosage for combined adminis¬tration is needed in clinical practice.
