Longitudinal monitoring of CYP3A activity in patients receiving 3 cycles of itraconazole pulse therapy for onychomycosis

Abstract

Itraconazole, a CYP3A inhibitor, is used for the treatment for onychomycosis with a three-cycle pulse therapy over 3months, but its effects on in vivo CYP3A activity during the entire course remain unknown. Urinary 6β-hydroxycortisol/cortisol ratios were determined in 19 patients with onychomycosis, before therapy, during three cycles of itraconazole pulse therapy (200mg twice daily for a week in each monthly cycle) and at 3month after completion of therapy. 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 3months post-treatment. The magnitude of inhibition appeared in proportion to the baseline CYP3A activity. 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 3weeks.