Pharmacokinetic behavior of micafungin in rats with carbon tetrachloride-induced acute hepatic failure

We examined the pharmacokinetic behavior of micafungin, a novel antifungal agent, in rats receiving carbon tetrachloride (CCl4) at a single dose of 2.5 ml/kg. There was no significant change in the total clearance (CL(tot)) in CCl4-treated rats, while the steady-state volume of distribution (Vd(ss)) was significantly increased by CCl4 treatment. Alteration in the serum unbound fraction of micafungin after CCl4 treatment was unlikely in light of the serum albumin, bilirubin, creatinine, and urea nitrogen. The increased Vd(ss) was attributable to augmentation in the accessibility of micafungin to peripheral tissue without impairment of the intrinsic clearance, because slight enhancement of the tissue distribution of micafungin was confirmed following CCl4 treatment.