@article{oai:kanazawa-u.repo.nii.ac.jp:00027053,
 author = {Ishizaki, Junko and Ito, Satsuki and Jin, Mingji and Shimada, Tsutomu and Ishigaki, Tamae and Harasawa, Yukiko and Yokogawa, Koichi and Takami, Akiyoshi and Nakao, Shinji and Miyamoto, Ken-ichi},
 issue = {4},
 journal = {Biopharmaceutics and Drug Disposition},
 month = {May},
 note = {The trough level of blood concentration of cyclosporin A (CyA) in a patient receiving immunotherapy was observed to decrease following coadministration of amphotericin B (AMB). This clinical observation was confirmed experimentally in Wistar rats intravenously given AMB (1.5 or 3.0 mg/kg) or saline (control) for 4 days, followed by CyA (10 mg/kg). The blood concentration of CyA after i.v. or p.o. administration in both AMB groups was significantly decreased compared with the control. The oral bioavailability of CyA after 1.5 or 3.0 mg/kg AMB treatment was decreased to 67% or 46%, respectively, of that of the control group. AMB treatment increased the expression levels of mdr1a and mdr1b mRNAs in the duodenum to about three times the control, and expression of CYP3A2 mRNA in the liver was increased to about twice the control. The P-gp and CYP3A2 proteins were increased significantly. These findings suggest that the oral bioavailability of CyA is reduced as a result of both increased efflux transport via P-glycoprotein in the duodenum and an increased first-pass effect of CYP3A2-mediated hepatic metabolic activity, induced by AMB. It is suggested that careful monitoring of CyA levels is necessary in the event of AMB administration to patients receiving immunotherapy with CyA. Copyright © 2008 John Wiley & Sons, Ltd., 金沢大学附属病院薬剤部},
 pages = {195--203},
 title = {Mechanism of decrease of oral bioavailability of cyclosporin a during immunotherapy upon coadministration of amphotericin B},
 volume = {29},
 year = {2008}
}