[Optimal dosages and cycles of itraconazole pulse therapy for onychomycosis].

OBJECTIVE

To compare the international standard regimen of itraconazole pulse therapy with low daily-dose 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 (200 mg/d, 3 cycles), Group II (200 mg/d, 6 cycles) or Group III (400 mg/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: 6,084 +/- 3,696 ng h/g; Group II: 10,448 +/- 6,980 ng h/g; Group III: 24,189 +/- 15,157 ng 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 400 mg/d itraconazole for 3 cycles was most effective. The significantly higher Group III AUC (week 48) 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.