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.