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

• Published in: DRUG METABOLISM AND PHARMACOKINETICS Vol. 20; no. 6; pp. 485 - 490
• Main Authors: Aoyama, Takahiko, Ogata, Kazuhiro, Shimizu, Makiko, Hatta, Shigeo, Masuhara, Keiso, Shima, Yoshinori, Kimura, Kenjirou, Matsumoto, Yoshiaki
• Format: Journal Article
• Language: English; Japanese
• Published: England Elsevier Ltd 2005; Japanese Society for the Study of Xenobiotics
• Subjects: Acute Kidney Injury - metabolism; Algorithms; Alkaline Phosphatase - metabolism; Animals; Antifungal Agents - administration & dosage; Antifungal Agents - pharmacokinetics; Area Under Curve; Chromatography, High Pressure Liquid; Data Interpretation, Statistical; fluconazole; Fluconazole - administration & dosage; Fluconazole - analogs & derivatives; Fluconazole - pharmacokinetics; fosfluconazole; Injections, Intraperitoneal; Injections, Intravenous; intraperitoneal administration; Male; Organophosphates - administration & dosage; Organophosphates - pharmacokinetics; peritoneal dialysis; Peritoneal Dialysis, Continuous Ambulatory; rat; Rats; Rats, Wistar; fosfluconazole; fluconazole; peritoneal dialysis; rat; intraperitoneal administration
• ISSN: 1347-4367; 1880-0920
• DOI: 10.2133/dmpk.20.485

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.