Ejects of Single and Repeated Treatment with Itraconazole on the Pharmacokinetics of Midazolam in Rats

To estimate the influence of repeated administration of drug metabolism inhibitors on the extent of drug interaction, we investigated the ejects of single intravenous or repeated oral administration of itraconazole on the pharmacokinetics of midazolam in rats. In the single administration study, the plasma concentration of itraconazole was maintained by intravenous infusion, and midazolam was administered into the portal vein to investigate its kinetics. In the repeated administration study, the kinetics of midazolam was investigated after seven-day oral treatment with itraconazole. The in vitro metabolism of midazolam and the contents of cytochrome P450 were investigated using liver microsomes from the itraconazole-treated rats.