Clinical and pharmacokinetic investigations of oral itraconazole in the treatment of onychomycosis

Abstract

A clinical study was carried out in 19 patients with onychomycosis in whom itraconazole was orally administered in a single daily dose of 100 mg. A follow-up period was instituted subsequent to the administration period to that the course of the nail lesions could be monitored. The concentrations of the drug in the plasma and in the nails were also determined. In patients in whom itraconazole was administered for 12-16 weeks, the decrease in the turbidity and thickening of the nails was maintained even after the administration period was completed. The efficacy rating in the overall evaluation at 12 weeks was 84.2% (16/19). In the evaluation performed at 24 weeks, the rating was 94.7% (18/19). These data indicate that the effect of itraconazole was maintained even after completion of the administration period. The retention of the drug in the nail after completion of the administration period was investigated in terms of the mean concentration of the drug in the nail with the passage of time in patients administered itraconazole for 10-16 weeks. It was found that a certain level of itraconazole was retained in the nail until at least the 24th week. Adverse reactions seen in this study consisted of diarrhoea and drug eruption, one case cach, and elevations of glutamic oxaloacetic transaminase and glutamic pyruvic transminase in one case.

Ultrastructural changes of Trichophyton rubrum in tinea unguium after itraconazole therapy in vivo observed using scanning electron microscopy

“…After therapy for only 3-4 months, the drug concentration in the nail plate is still high over the following 3-6 months. [6][7][8][9] Therefore, patients with onychomycosis are recommended to undergo treatment for only 3-4 months but to continue monitoring the recovery for the next 6 months. Itraconazole (ICZ) 9,10 is a broad-spectrum antifungal drug that inhibits the growth of fungi by interfering with the synthesis of ergosterol in the cell membrane, thereby causing membrane leakage, reproductive failure and slow death of the fungus.…”

Pharmacokinetics and bioavailability of itraconazole oral solution in cats

“…The volume of distribution (corrected for bioavailability) after PO administration (15.1 ± 4.41 l/kg) was larger than that of IV administration (8.51 ± 1.92 l/kg) in cats and PO administration in horses (6.30 ± 0.94 l/kg). The large volume of distribution (corrected for bioavailability) observed after PO administration was likely due to ITR's extensive distribution to nail, skin and tissue, 17 and its slow release from peripheral tissue to the blood. In the present study, the oral solution bioavailability in fasted cats was only 52.1 ± 11.6%, which is lower than in horses (65.0 ± 26.3%) 16 and in non-fasted cats (78.8 ± 28.0%).…”

One week pulse therapy with itraconazole (200 mg day−1) for onychomycosis. Evaluation of treatment results according to patient background

“…Infected fingernails as well as toenails from among the first to third fingers showing the highest degree of turbidity were subjected to testing. A given nail was judged to be turbid when the length between the distal edge of the nail bed and the posterior nail fold was rated 10 [10]. In addition, the following patient backgrounds were described: (1) age; (2) sex; (3) occupation (classified into two groups as blue‐collar workers engaged in work that created a strain on toenails or fingernails and white‐collar workers); (4) duration of the disease; (5) site of the lesion (fingernail or toenail); (6) clinical types [distal lateral subungual onychomycosis (DLSO), proximal subungual onychomycosis (PSO), superficial white onychomycosis (SWO), total dystrohic onychomycosis (TDO)]; (7) the number of affected nails (excepting the fifth toenail), severity of thickening (4 grades, 0: no‐thickening, 1: mild, 2: moderate, 3: severe), presence or absence of pathogens; and (8) underlying disease (with or without adult diseases and so on).…”

“…In Japan, however, the administration of daily 400 mg doses of itraconazole lasting 1 week is not allowed due to health insurance regulations because of the prohibitively high cost of the drug; at the same time, this dosage is considered by many medical professionals in Japan to be excessive. As a result, pulse therapy using daily doses of 200 mg of itraconazole for 1 week is prescribed instead [8–12]. In the present study, we employed pulse therapy using daily 200 mg doses of itraconazole and evaluated treatment results as well as assessed factors in the patients' background that may have affected the results.…”