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, C_max 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.

• Dasatinib
• imatinib
• interaction
• pharmacokinetic
• rat

Declaration of interest

The authors declare no conflict of interest.

This work was supported by a grant funded by the Association of Integrated Traditional and Western Medicine Research Project of Zhejiang Province (2013LYSX014).