Longitudinal monitoring of CYP3A activity in patients receiving 3 cycles of itraconazole pulse therapy for onychomycosis. (10th January 2014)

• Record Type: Journal Article
• Authors: Shibata, S.; Takahashi, H.; Ono, N.; Wada, N.; Kubo, H.; Shinozaki, K.; Saito, H.; Inamoto, N.; Machida, M.; Atsuda, K.; Echizen, H.
• Is Part Of: Journal of clinical pharmacy and therapeutics. Volume 39:Number 2(2014:Apr.)
• Page Start: 181
• Page End: 185
• Publication Date: 2014-01-10
• Subjects: Clinical pharmacology -- Periodicals; Chemotherapy -- Periodicals; 615
• DOI: 10.1111/jcpt.12127
• Languages: English
• ISSNs: 0269-4727

Abstract

<abstract abstract-type="main" id="jcpt12127-abs-0001"> <title>Summary</title> <sec id="jcpt12127-sec-0001" sec-type="section"> <title>What is known and objective</title> <p>Itraconazole, a CYP3A inhibitor, is used for the treatment for onychomycosis with a three‐cycle pulse therapy over 3 months, but its effects on <italic>in vivo </italic>CYP3A activity during the entire course remain unknown.</p> </sec> <sec id="jcpt12127-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="jcpt12127-sec-0003" sec-type="section"> <title>Results and discussion</title> <p>The mean 6β‐hydroxycortisol/cortisol ratio was reduced by 68% from baseline (<italic>P</italic> < 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.</p> </sec> <sec id="jcpt12127-sec-0004" sec-type="section"> <title>What is new and conclusion</title> <p>The inhibitory effect of itraconazole pulse therapy on the <italic>in vivo </italic>CYP3A activity appears clinically relevant at the end of each cycle, but the inhibition resolves, on average, within 3 weeks.</p> </sec> </abstract>