Pharmacokinetics of Fluconazole and Fosfluconazole after Intraperitoneal Administration to Peritoneal Dialysis Rats

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  • AOYAMA Takahiko
    Department of Clinical Pharmacology and Toxicology, Showa Pharmaceutical University
  • OGATA Kazuhiro
    Department of Clinical Pharmacology and Toxicology, Showa Pharmaceutical University
  • SHIMIZU Makiko
    Department of Clinical Pharmacology and Toxicology, Showa Pharmaceutical University
  • HATTA Shigeo
    Department of Pharmacy, St. Marianna University, School of Medicine and Hospital
  • MASUHARA Keiso
    Department of Pharmacy, St. Marianna University, School of Medicine and Hospital
  • SHIMA Yoshinori
    Division of Nephrology and Hypertension, St. Marianna University, School of Medicine
  • KIMURA Kenjirou
    Division of Nephrology and Hypertension, St. Marianna University, School of Medicine
  • MATSUMOTO Yoshiaki
    Department of Clinical Pharmacology and Toxicology, Showa Pharmaceutical University College of Pharmacy, Nihon University

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   Fluconazole (FLCZ) is an antifungal agent that is efficacious in the treatment of fungal peritonitis. Fosfluconazole (F-FLCZ) is the phosphate prodrug of FLCZ, which is highly soluble compared with FLCZ. F-FLCZ is useful against fungal peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients because it has a high water solubility. The aims of the present study were to characterize the peritoneal permeability of FLCZ and the pharmacokinetics of FLCZ and F-FLCZ after intraperitoneal (i.p.) administration to peritoneal dialysis rats. FLCZ or F-FLCZ was administered intravenously and intraperitoneally. After the i.p. administration of F-FLCZ, FLCZ was detected in circulating blood and the dialyzing fluid in peritoneal dialysis rats. The concentration of plasma FLCZ after the i.p. F-FLCZ administration was lower than that after the intravenous (i.v.) F-FLCZ administration. It is considered that the dose should be increased appropriately when F-FLCZ is administered intraperitoneally. The profiles of plasma FLCZ after i.v. and i.p. administrations were analyzed using a two-compartment model in which the distribution volume of the peripheral compartment was fixed at a volume of the dialyzing fluid (peritoneal dialysis PK model). The peritoneal dialysis PK model could describe the profiles of plasma and dialyzing fluid FLCZ. These results suggest that FLCZ and F-FLCZ could be administered intraperitoneally for the treatment of fungal peritonitis in CAPD patients.<br>

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