title: Pharmacokinetic behavior of micafungin in rats with carbon tetrachloride-induced acute hepatic failure.
abstract: 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.
authors.affiliation: Department of Hospital Pharmacy, Shiga University of Medical Science, Seta, Otsu, Japan. konishi@belle.shiga-med.ac.jp
authors.forename: Hiroki
authors.initials: H
authors.lastname: Konishi
authors.forename: Masatomo
authors.initials: M
authors.lastname: Sudo
authors.forename: Masaki
authors.initials: M
authors.lastname: Sumi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Morii
authors.forename: Tokuzo
authors.initials: T
authors.lastname: Minouchi
authors.forename: Tachio
authors.initials: T
authors.lastname: Aimoto
authors.forename: Akira
authors.initials: A
authors.lastname: Yamaji
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D054714:Echinocandins; D007275:Injections, Intravenous; D055666:Lipopeptides; D008074:Lipoproteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D017114:Liver Failure, Acute / Q000097:blood* / Q000139:chemically induced; D008297:Male; D000077551:Micafungin; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D002251:Carbon Tetrachloride; D000077551:Micafungin