I.v. fentanyl decreases the clearance of midazolam

We have examined the effect of fentanyl on the pharmacokinetics of midazolam in patients undergoing orthopaedic surgery. Thirty patients were allocated randomly to receive fentanyl 200 micrograms and midazolam 0.2 mg kg-1 (fentanyl group, n = 15) or placebo and midazolam 0.2 mg kg-1 (placebo group, n = 15) in a double-blind manner for induction of anaesthesia. Anaesthesia was maintained with nitrous oxide and isoflurane. Systemic clearance of midazolam was decreased by 30% (P = 0.002) and elimination half-time was prolonged by 50% (P = 0.04) in the fentanyl group compared with the placebo group. There were no differences in the distribution half-time or volume of distribution at steady state between the two groups. These findings indicate that elimination of midazolam was inhibited by fentanyl during general anaesthesia.