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

Drug Dev Ind Pharm. 2015;41(12):1948-53. doi: 10.3109/03639045.2015.1004182. Epub 2015 Jan 30.

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.

Keywords: Dasatinib; imatinib; interaction; pharmacokinetic; rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Chromatography, High Pressure Liquid / methods
  • Dasatinib / administration & dosage
  • Dasatinib / analysis*
  • Dasatinib / pharmacokinetics*
  • Drug Combinations
  • Drug Interactions / physiology
  • Imatinib Mesylate / administration & dosage
  • Imatinib Mesylate / analysis*
  • Imatinib Mesylate / pharmacokinetics*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Tandem Mass Spectrometry / methods*

Substances

  • Drug Combinations
  • Imatinib Mesylate
  • Dasatinib