Pharmacokinetics of micafungin in patients undergoing allogeneic hematopoietic stem cell transplantation

Abstract

Micafungin (MCFG) is an antifungal agent that is widely used for the treatment of invasive fungal infection. Although the pharmacokinetics of MCFG is considered to depend on the hepatic metabolism, the impact of hepatic function on the pharmacokinetics of MCFG has been inconsistent among previous studies. The object of this study was to evaluate the relationship between plasma MCFG concentration and clinical and laboratory data. We examined the plasma concentration of MCFG in 10 patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT). MCFG at 150mg/day was administered intravenously a median of 58.5days after HSCT. Trough and peak concentrations of MCFG (Cmin and Cmax) were measured at a median of 5.5days after the first administration of MCFG. The presence of graft-versus-host disease involving the liver at blood sampling was associated with significantly higher Cmin and Cmax of MCFG. Among the laboratory data, Cmin and Cmax were significantly higher in patients with severely impaired hepatic function defined as serum total bilirubin (TBi) level >5mg/dL and/or serum gamma-glutamyltransferase (γ-GTP) level >500IU/L, but the presence of mildly impaired hepatic function defined as serum TBi level >2mg/dL and/or serum γ-GTP level >200IU/L did not affect Cmin and Cmax. Renal function did not show significant impact on Cmin and Cmax. These findings suggest that the pharmacokinetics of MCFG is affected only by severely impaired liver function.