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Itraconazole moderately increases serum concentrations of oxybutynin but does not affect those of the active metabolite.

Author(s): Lukkari E, Juhakoski A, Aranko K, Neuvonen PJ

Affiliation(s): Department of Clinical Pharmacology, University of Helsinki, Finland.

Publication date & source: 1997, Eur J Clin Pharmacol., 52(5):403-6.

Publication type: Clinical Trial; Randomized Controlled Trial

OBJECTIVE: Oxybutynin has low oral bioavailability due to an extensive presystemic metabolism. It has been suggested that the biotransformation of oxybutynin is dependent on CYP3A. Because itraconazole, a widely used mycotic, is a potent inhibitor of CYP3A4, we wanted to study a possible interaction between oxybutynin and itraconazole. METHODS: In this double-blind, randomized, two-phase cross-over study, ten healthy volunteers received either 200 mg itraconazole or placebo for 4 days. On day 4, each volunteer ingested a single dose of 5 mg oxybutynin. Serum concentrations of oxybutynin, its active metabolite N-desethyloxybutynin, and itraconazole were monitored over 24 h. RESULTS: Itraconazole significantly increased both the area under the serum drug concentration-time curve (AUC0-t) and the peak concentration of oxybutynin twofold. The AUC0-t and the peak concentration of N-desethyloxybutynin were not significantly affected by itraconazole. Itraconazole did not change the peak time or the elimination half-life of either oxybutynin or N-desethyloxybutynin. The occurrence of adverse events after oxybutynin administration was not increased by itraconazole. CONCLUSIONS: Itraconazole moderately increases serum concentrations of oxybutynin, probably by inhibiting the CYP3A-mediated metabolism. However, the concentrations of N-desethyloxybutynin were practically unchanged. Since about 90% of the antimuscarinic activity of oxybutynin is attributable to N-desethyloxybutynin, any interaction of oxybutynin with CYP3A4 inhibiting drugs has only minor clinical significance.

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