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

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, Gilberto De Nucci.

Journal Name: Anti-Infective Agents
Anti-Infective Agents in Medicinal Chemistry

Volume 16 , Issue 1 , 2018

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Graphical 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.

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

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Article Details

Year: 2018
Page: [15 - 21]
Pages: 7
DOI: 10.2174/2211352515666171124160816
Price: $25

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