Pharmacokinetic interaction study of combining imatinib with dasatinib in rats by UPLC-MS/MS.

ABSTRACT

This study examined whether oral administration of dasatinib to the rats with imatinib led to any pharmacokinetic interactions. Twenty-four rats were divided randomly into three groups, imatinib group (imatinib 25 mg/kg, n = 8), dasatinib group (dasatinib 15 mg/kg, n = 8) and co-administration group (dasatinib 15 mg/kg and imatinib 25 mg/kg, n = 8). The concentration of imatinib and dasatinib in rat plasma was determined by a sensitive and simple UPLC-MS/MS method. There was statistical pharmacokinetics difference for imatinib in the imatinib group and co-administration group, when co-oral administration imatinib with dasatinib, MRT(0-t) increased (p < 0.01). There was statistical pharmacokinetics difference for dasatinib in the dasatinib group and co-administration group, when co-oral administration dasatinib with imatinib, Cmax and AUC increased (p < 0.01), CL and V decreased (p < 0.01). These data indicate dasatinib could slightly influence the pharmacokinetic profile of imatinib in rats, and imatinib could influence the pharmacokinetic profile of dasatinib in rats, which might cause drug-drug interactions when using imatinib with dasatinib.