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Pharmacokinetics of antifungal agents
A Fabris1, M V Pellanda, C Gardin
1Nephrology and Dialysis Service, Ospedale Di Bassano Del Grappa, Italy.
Abstract:
The authors have evaluated the pharmacokinetics of four antifungal agents used in the therapy of fungal peritonitis. Amphotericin B (Amph B) poorly diffuses from blood into peritoneal fluid, which intraperitoneal administration induces severe abdominal pain. 5-Fluorocytosine (5FC) easily crosses peritoneum, but resistance may appear when the drug is used alone. Ketoconazole (K) poorly penetrates into peritoneal fluid, while Fluconazole (F), used per os or intraperitoneally, shows a good antifungal activity both in serum and in the peritoneal fluid. In conclusion, from a pharmacokinetic point of view, all the antifungal agents examined, perhaps with the exception of F, do not offer, when used alone, sufficient guarantees in curing peritonitis. Therefore, for treating fungal infections in CAPD, drug combinations such as AmphB + 5FC, K + 5FC or 5FC+F have to be used.
Insights
Pharmacokinetics of antifungal agents for fungal peritonitis reveal that Fluconazole is promising, but combinations like Amphotericin B + 5-Fluorocytosine are necessary for effective treatment.
Area of Science:
- Pharmacology
- Infectious Diseases
- Nephrology
Background:
- Fungal peritonitis is a serious complication in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).
- Effective management requires antifungal agents with adequate peritoneal penetration and efficacy.
Purpose of the Study:
- To evaluate the pharmacokinetics of four antifungal agents for treating fungal peritonitis.
- To determine the suitability of monotherapy versus combination therapy for fungal peritonitis.
Main Methods:
- Pharmacokinetic evaluation of Amphotericin B, 5-Fluorocytosine, Ketoconazole, and Fluconazole.
- Assessment of drug diffusion into peritoneal fluid and serum activity.
Main Results:
- Amphotericin B shows poor peritoneal penetration; 5-Fluorocytosine penetrates well but risks resistance.
- Ketoconazole has limited peritoneal penetration; Fluconazole demonstrates good activity in both serum and peritoneal fluid.
- Monotherapy with most agents, except possibly Fluconazole, is insufficient for treating fungal peritonitis.
Conclusions:
- Antifungal monotherapy, with potential exception of Fluconazole, is inadequate for fungal peritonitis based on pharmacokinetics.
- Combination therapies, including Amphotericin B + 5-Fluorocytosine, Ketoconazole + 5-Fluorocytosine, or 5-Fluorocytosine + Fluconazole, are recommended for treating fungal infections in CAPD patients.