Premium
Longitudinal monitoring of CYP 3A activity in patients receiving 3 cycles of itraconazole pulse therapy for onychomycosis
Author(s) -
Shibata S.,
Takahashi H.,
Ono N.,
Wada N.,
Kubo H.,
Shinozaki K.,
Saito H.,
Inamoto N.,
Machida M.,
Atsuda K.,
Echizen H.
Publication year - 2014
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.12127
Subject(s) - itraconazole , dosing , cyp3a , medicine , in vivo , pharmacokinetics , pulse (music) , pharmacology , endocrinology , antifungal , biology , dermatology , metabolism , microbiology and biotechnology , cytochrome p450 , detector , electrical engineering , engineering
Summary What is known and objective Itraconazole, a CYP 3A inhibitor, is used for the treatment for onychomycosis with a three‐cycle pulse therapy over 3 months, but its effects on in vivo CYP 3A 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. Results and discussion 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 CYP 3A activity. What is new and conclusion The inhibitory effect of itraconazole pulse therapy on the in vivo CYP 3A activity appears clinically relevant at the end of each cycle, but the inhibition resolves, on average, within 3 weeks.