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

Autor: Campos R; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil., Bittencourt SF; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil; Galeno Research Unit, Latino Coelho St., 1301, Parque Taquaral, 13087-010 Campinas, SP, Brazil., Rojas-Moscoso JA; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil., Pissinatti L; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil., Chen LS; Galeno Research Unit, Latino Coelho St., 1301, Parque Taquaral, 13087-010 Campinas, SP, Brazil., Porto M; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil., Moreno RA; Galeno Research Unit, Latino Coelho St., 1301, Parque Taquaral, 13087-010 Campinas, SP, Brazil., Mendes GD; Galeno Research Unit, Latino Coelho St., 1301, Parque Taquaral, 13087-010 Campinas, SP, Brazil; Faculty of Medical Sciences, São Leopoldo Mandic, São Paulo, Brazil; Department of Pharmacology, Faculty of Medicine, Brazil University, Fernandópolis, Brazil., De Nucci G; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil; Galeno Research Unit, Latino Coelho St., 1301, Parque Taquaral, 13087-010 Campinas, SP, Brazil; Faculty of Medical Sciences, São Leopoldo Mandic, São Paulo, Brazil. Electronic address: denucci@gilbertodenucci.com.
Jazyk: angličtina
Zdroj: Journal of pharmacological and toxicological methods [J Pharmacol Toxicol Methods] 2018 Nov - Dec; Vol. 94 (Pt 1), pp. 14-18. Date of Electronic Publication: 2018 Apr 07.
DOI: 10.1016/j.vascn.2018.04.001
Abstrakt: 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.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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