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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Drug Metabolism and Transport
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1515462
This article is part of the Research Topic ADME of Drugs to Treat Infectious Diseases View all 4 articles

Amphotericin B Tissue Penetration and Pharmacokinetics in Healthy and Candida albicans-Infected Rats: Insights from Microdialysis and Population Modeling

Provisionally accepted
Valdeene Vieira Santos Valdeene Vieira Santos 1Laiz Campos Pereira Laiz Campos Pereira 1Jackeline Marley Santos de Araujo Jackeline Marley Santos de Araujo 1Matheus Antonio da Hora Borges Matheus Antonio da Hora Borges 1Carolina Magalhaes Brandao Carolina Magalhaes Brandao 1Luisa Oliveira Santos Luisa Oliveira Santos 1Cristiane Flora Villarreal Cristiane Flora Villarreal 1Francine Johansson Azeredo Francine Johansson Azeredo 2*
  • 1 Federal University of Bahia (UFBA), Salvador, Bahia, Brazil
  • 2 University of Florida, Gainesville, United States

The final, formatted version of the article will be published soon.

    This study, which evaluated the relationship between total plasma and free kidney concentrations of AmB in healthy and C. albicans-infected Wistar rats using microdialysis, has the potential to significantly impact future research in the field and improve the development of antifungal drugs. The findings of this study, which show that plasma levels are a good predictor for AmB kidney concentrations and can be used to optimize its dosing regimen, underscore the importance of this research. Microdialysis probe recovery rates were determined by dialysis and retrodialysis in vitro, as well as by retrodialysis in vivo. The intravenous (i.v) administration of 2.5 x 10 6 CFU/ml of C. albicans ATCC induced the infection. 2.5 mg/kg i.v. bolus in healthy and C. albicans-infected rats (n = 6/group). Plasma and microdialysate samples were analyzed using HPLC-diode-array detection. AmB tissue penetration was analyzed using the ratio between total plasma and kidney and population pharmacokinetics (PopPK) to assess the impact of the infection on pharmacokinetic parameters. The chosen flow rate was set to 1.5 µL/min, and there was no statistical difference between the relative recovery values when changing AmB concentrations. The in vivo relative recovery was determined to be 10.9 ± 3.7 %. The antifungal tissue penetration was 0.77 and 0.71 for healthy and infected animals, respectively. The structural PK model with two compartments and linear elimination describes the concentration versus time profile of AmB simultaneously in plasma and tissue. Infection by C. albicans does not interfere with AmB kidney penetration. AmB protein binding is demonstrated to be nonlinear, dependent on AmB concentration in healthy and infected animals' plasma.

    Keywords: Amphotericin B1, Candida albicans2, population pharmacokinetic modeling3, microdialysis4, rats5

    Received: 22 Oct 2024; Accepted: 13 Dec 2024.

    Copyright: © 2024 Santos, Pereira, de Araujo, Borges, Brandao, Santos, Villarreal and Azeredo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Francine Johansson Azeredo, University of Florida, Gainesville, United States

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