Naftifine

Naftifine is a topical antifungal drug.

The pharmacodynamics of naftifine gel have not been established.

In vitro and in vivo bioavailability studies have demonstrated that naftifine penetrates the stratum corneum in sufficient concentration to inhibit the growth of dermatophytes.

Pharmacokinetic analysis of plasma samples from 32 subjects with tinea pedis treated with a mean dose of 3.9 grams naftifine gel applied once daily to both feet for 14 days showed increased exposure over the treatment period, with a geometric mean (CV%) AUC_0-24 (area under plasma concentration-versus-time curve from time 0 to 24 hours) of 10.5 (118) ng∙hr/mL on Day 1 and an AUC_0-24 of 70 (59) ng∙hr/mL on Day 14. The accumulation ratio based on AUC was approximately 6.

Maximum concentration (C_max) also increased over the treatment period; geometric mean (CV%) C_max after a single dose was 0.9 (92) ng/mL on Day 1; C_max on Day 14 was 3.7 (64) ng/mL. Median T_max was 20.0 hours (range: 8, 20 hours) after a single application on Day 1 and 8.0 hours (range: 0, 24 hours) on Day 14. Trough plasma concentrations increased during the trial period and reached steady state after 11 days. In the same pharmacokinetic trial the fraction of dose excreted in urine during the treatment period was less than or equal to 0.01% of the applied dose.

In a second trial, the pharmacokinetics of naftifine gel was evaluated in 22 pediatric subjects 12-17 years of age with tinea pedis. Subjects were treated with a mean dose of 4.1 grams naftifine gel applied to the affected area once daily for 14 days. The results showed that the systemic exposure increased over the treatment period. Geometric mean (CV%) AUC_0-24 was 15.9 (212) ng∙hr/mL on Day 1 and 60.0 (131) ng∙hr/mL on Day 14. Geometric mean (CV%) C_max after a single dose was 1.40 (154) ng/mL on Day 1 and 3.81 (154) ng/mL on Day 14. The fraction of dose excreted in urine during the treatment period was less than or equal to 0.003% of the applied dose.