title: Itraconazole moderately increases serum concentrations of oxybutynin but does not affect those of the active metabolite.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, University of Helsinki, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Lukkari
authors.forename: A
authors.initials: A
authors.lastname: Juhakoski
authors.forename: K
authors.initials: K
authors.lastname: Aranko
authors.forename: P J
authors.initials: PJ
authors.lastname: Neuvonen
mesh_terms: D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004357:Drug Synergism; D005260:Female; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology*; D008297:Male; D008333:Mandelic Acids / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D000935:Antifungal Agents; D018680:Cholinergic Antagonists; D008333:Mandelic Acids; D017964:Itraconazole; C032681:desethyloxybutynin; C005419:oxybutynin