Drug–Drug Interactions Of Amiodarone And Quinidine On The Pharmacokinetics Of Eliglustat In Rats

BACKGROUND: 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), AUC(0→∞), and C(max)) 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.