Pharmacokinetic interaction of ketoconazole and itraconazole with ciprofloxacin

The effect of the concomitant administration of the antifungal drugs ketoconazole (KTC) and itraconazole (ITC) on the pharmacokinetics of ciprofloxacin (CIP) following short- and long-term administration in mice was investigated. Animals received either a dose of CIP (20 mg/kg, i.p.), CIP (20 mg/kg, i.p.) together with KTC (50 mg/kg, p.o.) or CIP (20 mg/kg, i.p.) and ITC (30 mg/kg, p.o.). The same treatments were repeated for 7 days. Blood samples were collected up to 4 h following drug administration and two urine samples were collected at 2 h and 4 h after drug administration. CIP plasma concentrations were significantly higher in KTC- and ITC-treated groups compared with the corresponding control groups. The concomitant administration of KTC or ITC with CIP also significantly (p<0.05) increased C(max), t(1/2), MRT and AUC(0-infinity) with no change in T(max). CIP clearance was significantly reduced by both agents. KTC and ITC reduced CIP urinary excretion. This study suggests that an important pharmacokinetic interaction between CIP and KTC or ITC is likely to occur when either of the two antifungal drugs is administered concomitantly with CIP. The results may suggest possible reductions in total clearance of CIP, owing to inhibition of its renal tubular excretion by KTC and ITC.