title: Longitudinal monitoring of CYP3A activity in patients receiving 3 cycles of itraconazole pulse therapy for onychomycosis.
abstract: OBJECTIVE
  Itraconazole, a CYP3A inhibitor, is used for the treatment for onychomycosis with a three-cycle pulse therapy over 3 months, but its effects on in vivo CYP3A activity during the entire course remain unknown.
  
  
  METHODS
  Urinary 6β-hydroxycortisol/cortisol ratios were determined in 19 patients with onychomycosis, before therapy, during three cycles of itraconazole pulse therapy (200 mg twice daily for a week in each monthly cycle) and at 3 month after completion of therapy.
  
  
  CONCLUSIONS
  The mean 6β-hydroxycortisol/cortisol ratio was reduced by 68% from baseline (P < 0·05) after the 1st pulse dosing, but the inhibitory effect appeared to be resolved before the next pulse dosing and at 3 months post-treatment. The magnitude of inhibition appeared in proportion to the baseline CYP3A activity.
  
  
  CONCLUSIONS
  The inhibitory effect of itraconazole pulse therapy on the in vivo CYP3A activity appears clinically relevant at the end of each cycle, but the inhibition resolves, on average, within 3 weeks.
authors.affiliation: Department of Pharmacy, Kitasato Institute Hospital, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Shibata
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: N
authors.initials: N
authors.lastname: Ono
authors.forename: N
authors.initials: N
authors.lastname: Wada
authors.forename: H
authors.initials: H
authors.lastname: Kubo
authors.forename: K
authors.initials: K
authors.lastname: Shinozaki
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: N
authors.initials: N
authors.lastname: Inamoto
authors.forename: M
authors.initials: M
authors.lastname: Machida
authors.forename: K
authors.initials: K
authors.lastname: Atsuda
authors.forename: H
authors.initials: H
authors.lastname: Echizen
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D065692:Cytochrome P-450 CYP3A Inhibitors; D016903:Drug Monitoring / Q000379:methods; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine; D017964:Itraconazole / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D014009:Onychomycosis / Q000188:drug therapy*; D020551:Pulse Therapy, Drug; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D017964:Itraconazole; C001380:6 beta-hydroxycortisol; D006854:Hydrocortisone
keywords: CYP3A; itraconazole; metabolic inhibition; onychomycosis; pulse therapy