The rabbit vagina as an in vivo model for vaginal fenticonazole permeability and toxicity.

INTRODUCTION

Vaginal route is often used in topical antifungal formulations. Vaginal permeability assays are generally performed as in vitro tests.

METHOD: An in vivo vaginal permeability assay was developed using female rabbits. Fenticonazole permeability was evaluated by assessing fenticonazole bioavailability in plasma by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS). Toxicity was monitored histopathologically after 8 consecutive days of antifungal treatment (20 mg/animal).

RESULTS

The method of quantification was linear with a lower limit of quantification (LLOQ) of (0.1 ng/mL). The area-under-the-curves (AUC) of fenticonazole on day 1 and 8 of treatment were 280.3 ± 86.1 ng/mL ∗ h and 805.7 ± 252.4 ng/mL ∗ h, respectively. The calculated systemic bioavailability was 12.73% ± 0.14%. No signs of toxicity were observed both macroscopically and histologically after 8 days fenticonazole treatment.

DISCUSSION: The plasma levels of fenticonazole observed in rabbits are similar to that observed in human. Rabbit vagina may be a suitable model to evaluate vaginal antifungal formulations.