Pharmacokinetics of Dapaconazole, A Novel Antifungal Agent, in Beagle Dogs and Inhibition of Cytochrome P450 Family 51

Title:Pharmacokinetics of Dapaconazole, A Novel Antifungal Agent, in Beagle Dogs and Inhibition of Cytochrome P450 Family 51

Volume: 16 Issue: 1

Author(s): Juliana S. Palo*, Noedi L. de Freitas, Samuel G.N.e Silva, Julio A. Rojas-Moscoso, Tiago Zaminelli, Caroline H. Lescano, Gustavo D. Mendes and Gilberto De Nucci

Affiliation:

• Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP,Brazil

Keywords: Azole antifungals, mass spectrometry, bioavailability, ketoconazole, tandem mass spectrometry, 14-α-demethylase.

Abstract: Objectives: Pharmacokinetics of dapaconazole and inhibition of cytochrome P450 family 51.

Methods: Pharmacokinetics of dapaconazole, a novel imidazolic antifungal compound, was studied in male beagle dogs following intravenous (1, 2 and 20 mg/kg) and oral (20 mg/kg) administration.

Results: Oral bioavailability was calculated to be 97.3%. The elimination half-life (t½) after intravenous administration was 2.1-2.5 h, the total body clearance was 2.5-4.2 L/h/kg and the apparent volume of distribution was 9.0-14.4 L/kg. Dapaconazole caused concentration-dependent inhibition of cytochrome P450 family 51 (CYP51) activity with an IC50 of 1.4 ± 0.3 μM (mean ± SEM, n=3), compared to that of ketoconazole (IC50 = 1.2 ± 0.6 μM, n=3).

Conclusion: Results indicate that dapaconazole could be a potentially useful drug for systemic administration.

Cite this article as:

Palo S. Juliana*, de Freitas L. Noedi , Silva G.N.e Samuel , Rojas-Moscoso A. Julio , Zaminelli Tiago , Lescano H. Caroline, D. Mendes Gustavo and De Nucci Gilberto, Pharmacokinetics of Dapaconazole, A Novel Antifungal Agent, in Beagle Dogs and Inhibition of Cytochrome P450 Family 51, Anti-Infective Agents 2018; 16 (1) . https://dx.doi.org/10.2174/2211352515666171124160816