Population pharmacokinetics of itraconazole in Japanese patients with invasive fungal peritonitis

Abstract

Severely ill patients are frequently at risk of developing fungal infection. Itraconazole (ITCZ), a triazole antifungal agent, is used for the treatment of candidiasis, aspergillosis, cryptococcosis. Correlation of pharmacokinetic and pharmacodynamic (PK-PD) parameters with the in vivo bactericidal action of antimicrobial agents has progressed markedly in recent years. However, the optimal dosage of antifungal agents based on PK-PD properties has not been clearly established. In this study, we performed a population pharmacokinetic analysis of ITCZ after infusion or oral administration of ITCZ in Japanese 51 patients with fungal infections. The population pharmacokinetic analysis was performed using NONMEM software. The population mean clearance (CL; liter/h) was estimated as 5.15-0.0673×(Age-62) L/h, the population mean volume of distribution (V; liter) was determined as 878L and the bioavailability (F) was determined as 0.665.