Effect of imatinib mesilate on the disposition kinetics of ciclosporin in rats.
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.
Kajita
Takashi
T
Department of Pharmacy, Tenri General Hospital, 200, Mishima-machi, Tenri 632-8552, Japan.
Higashi
Yasuhiko
Y
Imamura
Masanobu
M
Maida
Chieko
C
Fujii
Youichi
Y
Yamamoto
Ikuyoshi
I
Miyamoto
Etsuko
E
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
D001549:Benzamides; D007166:Immunosuppressive Agents; D010879:Piperazines; D011743:Pyrimidines; D016572:Cyclosporine; D000068877:Imatinib Mesylate