Drug Design, Development and Therapy (Dec 2019)
Drug–Drug Interactions Of Amiodarone And Quinidine On The Pharmacokinetics Of Eliglustat In Rats
Abstract
Qiong Wang,1 Haiyun Wang,1 Youyan Zhong,1 Qiang Zhang2 1Department of Pharmacy, Wenzhou People’s Hospital, Wenzhou, Zhejiang 325000, People’s Republic of China; 2Department of Clinical Laboratory, The People’s Hospital of Lishui, Lishui, Zhejiang 323000, People’s Republic of ChinaCorrespondence: Qiang ZhangDepartment of Clinical Laboratory, The People’s Hospital of Lishui, Lishui, Zhejiang 323000, People’s Republic of ChinaEmail [email protected]: Eliglustat, a new oral substrate-reduction therapy, was recently approved as a first-line therapy for Gaucher’s disease type 1 (GD1) patients.Purpose: The purpose of the present study was to develop and validate a simple UPLC-MS/MS method for the measurement of plasma-eliglustat concentration and to investigate the effects of amiodarone and quinidine on eliglustat metabolism in rats.Methods: Eighteen rats were randomly divided into three groups (n=6): control (0.5% CMC-Na, group A), amiodarone (60 mg/kg, group B), and quinidine (100 mg/kg, group C). Thirty minutes later, 10 mg/kg eliglustat was orally administered to each rat and concentrations of eliglustat in the rats determined by our UPLC-MS/MS method.Results: Amiodarone and quinidine increased the main pharmacokinetic parameters (AUC0→t, AUC0→∞, and Cmax) of eliglustat significantly and decreased clearance obviously.Conclusion: Amiodarone and quinidine can elevate eliglustat exposure and have an inhibitory effect on eliglustat metabolism. Clearly, appropriate pharmacological studies of eliglustat in patients treated with amiodarone or quinidine should be done in future.Keywords: eliglustat, drug–drug interaction, UPLC-MS/MS, amiodarone, quinidine
