LACK OF EFFECT OF ANTIMYCOTIC ITRACONAZOLE ON THE PHARMACOKINETICS ORPHARMACODYNAMICS OF TEMAZEPAM

The azole antimycotics itraconazole and ketoconazole are potent and re latively nonspecific inhibitors of cytochrome P450 enzymes and have a potentially dangerous interaction with midazolam and triazolam. The po ssible interaction between itraconazole and a short-acting benzodiazep ine, temazepam, was investigated in a double-blind, randomized crossov er study. Ten healthy volunteers were given placebo or 200 mg itracona zole a day orally for 4 days. The challenge dose of 20 mg of temazepam was ingested on the fourth day, after which plasma samples were colle cted, and psychomotor performance tests were carried out for 24 h. Des pite a statistically significant small increase of the area under the temazepam concentration-time curve, there was no clinically significan t interaction, as determined by the psychomotor performance tests. The different metabolic pathways and the lack of significant first-pass m etabolism of temazepam explain the great difference in the interaction potential of temazepam compared with midazolam and triazolam. Temazep am, unlike midazolam and triazolam, can be prescribed in usual doses f or patients receiving itraconazole and other inhibitors of P450 3A4.