title: 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.
authors: a The Laboratory of Clinical Pharmacy , People's Hospital of Lishui City, Wenzhou Medical University , Lishui , China .
authors: Yunfang
authors: Y
authors: Zhou
authors: a The Laboratory of Clinical Pharmacy , People's Hospital of Lishui City, Wenzhou Medical University , Lishui , China .
authors: Shuanghu
authors: S
authors: Wang
authors: a The Laboratory of Clinical Pharmacy , People's Hospital of Lishui City, Wenzhou Medical University , Lishui , China .
authors: Ting
authors: T
authors: Ding
authors: a The Laboratory of Clinical Pharmacy , People's Hospital of Lishui City, Wenzhou Medical University , Lishui , China .
authors: Mingdong
authors: M
authors: Wu
authors: a The Laboratory of Clinical Pharmacy , People's Hospital of Lishui City, Wenzhou Medical University , Lishui , China .
authors: Peiwu
authors: P
authors: Geng
authors: b Shanghai Institute of Pharmaceutical Industry , Shanghai , China , and.
authors: Qingwei
authors: Q
authors: Zhang
authors: c Function Experiment Teaching Center, Wenzhou Medical University , Wenzhou , China.
authors: Jianshe
authors: J
authors: Ma
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D000069439:Dasatinib / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics*; D004338:Drug Combinations; D004347:Drug Interactions / Q000502:physiology; D000068877:Imatinib Mesylate / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004338:Drug Combinations; D000068877:Imatinib Mesylate; D000069439:Dasatinib
keywords: Dasatinib; imatinib; interaction; pharmacokinetic; rat