title: Effect of imatinib mesilate on the disposition kinetics of ciclosporin in rats.
abstract: The purpose of this study was to investigate the effect of imatinib mesilate on the disposition kinetics of ciclosporin in rats. The blood concentration-time course and pharmacokinetic parameters of ciclosporin did not significantly change after intravenous injection of ciclosporin (10 mg kg(-1)) in rats treated with imatinib mesilate (50 mg kg(-1)) as compared with a control. When ciclosporin (10 mg kg(-1)) was orally administered, the time course, area under the curve, bioavailability and peak blood concentration of ciclosporin were significantly increased in rats that had been treated with imatinib mesilate 2 h before ciclosporin administration as compared with the control. Because both drugs are transported via P-glycoprotein and breast cancer resistance protein and metabolized by cytochrome P450 3A2, the interaction of imatinib mesilate with these proteins may be responsible for the increased intestinal absorption of ciclosporin in rats. These results indicate that imatinib mesilate enhanced the intestinal absorption of ciclosporin in rats with only the oral administration of ciclosporin, suggesting that our results support clinical data. In addition, imatinib mesilate may increase the pharmacological effects and possibly toxicity of ciclosporin.
authors.affiliation: Department of Pharmacy, Tenri General Hospital, 200, Mishima-machi, Tenri 632-8552, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kajita
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Higashi
authors.forename: Masanobu
authors.initials: M
authors.lastname: Imamura
authors.forename: Chieko
authors.initials: C
authors.lastname: Maida
authors.forename: Youichi
authors.initials: Y
authors.lastname: Fujii
authors.forename: Ikuyoshi
authors.initials: I
authors.lastname: Yamamoto
authors.forename: Etsuko
authors.initials: E
authors.lastname: Miyamoto
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001549:Benzamides; D001682:Biological Availability; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D000068877:Imatinib Mesylate; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D001549:Benzamides; D007166:Immunosuppressive Agents; D010879:Piperazines; D011743:Pyrimidines; D016572:Cyclosporine; D000068877:Imatinib Mesylate