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British Journal of Anaesthesia, Vol 81, Issue 4 598-600, Copyright © 1998 by The Board of Management and Trustees of the British Journal of Anaesthesia

SHORT COMMUNICATIONS

The CYP 3A4 inhibitor itraconazole has no effect on the pharmacokinetics of i.v. fentanyl

V. J. Palkama, P. J. Neuvonen and K. T. Olkkola
Departments of Anaesthesia and Clinical Pharmacology, University of Helsinki, PO Box 260, FIN-00029 HYKS, Finland

We studied 10 healthy volunteers given itraconazole 200 mg orally, once daily or placebo for 4 days in a crossover study. i.v. fentanyl 3 micrograms kg-1 was given on day 4. Plasma concentrations of fentanyl were measured by radioimmunoassay and ventilatory frequency and peripheral arteriolar oxygen saturation were also measured. Fentanyl- induced subjective effects (drowsiness, itching, nausea, performance, feeling of drug effect) were measured by visual analogue scales. The pharmacokinetics and pharmacodynamics of fentanyl were similar after both itraconazole and placebo. Thus although itraconazole is a strong inhibitor of the cytochrome 3A enzymes responsible for metabolism of fentanyl in vitro, it did not affect the i.v. pharmacokinetics of fentanyl in humans.
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