Abstract
Objective: To compare the international standard regimen of itraconazole pulse therapy with low dailydose pulse therapies, which are widely conducted in Japan.
Design: Randomized, double-blind, parallel-group comparative study.
Patients: 186 patients with a big toenail showing onychomycosis symptoms such as opacity.
Intervention: Patients were assigned to Group I (200mg/d, 3 cycles), Group II (200mg/d, 6 cycles) or Group III (400mg/d, 3 cycles). All received itraconazole orally.
Main Outcome Measure: Cure or complete response-assessment based on improvement in the opacity ratio and microscopic examination.
Results: The clinical response rates (cure plus complete response) at week 24 were Group I: 14.9%;Group II: 25.5%; Group III: 32.7%. At week 48, 17 patients were cured in Group III-up from 3 at week 24. At week 48 the area under the nail plate concentration-time curves (AUC) was: Group I: 6084±3696ng·h/g; Group II: 10448±6980ng·h/g; Group III: 24189±15157ng·h/g. There was no difference among the three groups in the incidence of adverse drug reactions.
Conclusions: The clinical response rates demonstrated that the pulse therapy of 400mg/d itraconazole for 3 cycles was most effective. The significantly higher Group III AUC (week 48) (p<0.01) suggests that, when the same total amount of itraconazole is administered, this drug remains in nail plates longer following pulse therapy with a higher daily dose. It was also suggested that clinical efficacy correlated with the duration of the presence of itraconazole.
