Pharmacokinetics of Fluconazole in the Serum and Exudate of the Pelvic Retroperitoneal Space after Radical Hysterectomy and Pelvic Lymphadenectomy

Abstract

The use of systemic antifungal agents has increased in recent years, partly as a result of the increasing incidence of compromised hosts. In gynaecology, the decision of which of these drugs to use has been a difficult one. The efficacies of these drugs depend on their antifungal spectra, potencies and tissue concentrations. This study investigated the pharmacokinetics of fluconazole in the serum and exudate of the retroperitoneal space that is formed after radical hysterectomy and pelvic lymphadenectomy. Fluconazole 200mg was administered to study patients for exactly 60 minutes using an automatic drip infusion pump. The parameters of the formulae analysed by the 2-compartment model were determined by the least-squares method, and a simulation curve was made. The maximum drug concentration (Cmax) of fluconazole in serum was 6.2 mg/L at 1.0 hour after beginning the drip infusion. The half-life of fluconazole in serum was very long, i.e. 17.7 hours after the start of the drip infusion. The area under the serum concentration-time curve (AUC) was 140.4 µg/ml·h. The Cmax of fluconazole in the exudate of the retroperitoneal space was 4.3 mg/L at 4.7 hours after the start of the drip infusion. The AUC in the exudate was 167.5 µg/ml·h. Fluconazole therefore appears to show considerable potential for attaining satisfactory tissue concentrations in the treatment of systemic fungal infections.