title: Effect of blood decrease on micafungin disposition in rats.
abstract: Micafungin (MCFG) is a novel echinocandin-class antifungal agent that extensively undergoes metabolic removal in the liver. In the present study, the influence of decreased blood volume on pharmacokinetic disposition of MCFG was examined using a rat model prepared by phlebotomy. In phlebotomized rats, hematocrit level and plasma albumin concentration were decreased by 50 and 15%, respectively. Regarding the pharmacokinetic parameters of MCFG, there were no significant differences in the total body clearance (CL(tot)) and elimination rate constant (k (e)) between control and phlebotomized rat groups. A slight increase was observed in the apparent volume of distribution at steady-state (Vd(ss)), but the degree of change was minimal. These findings demonstrate that the elimination capacity for MCFG is only slightly affected by severe anemia and moderate hypoalbuminemia, and provide experimental evidence for the preceding clinical studies suggesting that neither hematocrit level nor serum albumin concentration is a contributory factor for the metabolic clearance of MCFG.
authors.affiliation: Laboratory of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, 548-8540, Japan. konishih@osaka-ohtani.ac.jp
authors.forename: Hiroki
authors.initials: H
authors.lastname: Konishi
authors.forename: Keizo
authors.initials: K
authors.lastname: Fukushima
authors.forename: Masatomo
authors.initials: M
authors.lastname: Sudo
authors.forename: Masaki
authors.initials: M
authors.lastname: Sumi
authors.forename: Tokuzo
authors.initials: T
authors.lastname: Minouchi
authors.forename: Ikumi
authors.initials: I
authors.lastname: Iga
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Shibata
authors.forename: Akira
authors.initials: A
authors.lastname: Yamaji
mesh_terms: D000740:Anemia / Q000378:metabolism*; D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics*; D054714:Echinocandins / Q000493:pharmacokinetics*; D034141:Hypoalbuminemia / Q000378:metabolism*; D055666:Lipopeptides / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D000077551:Micafungin; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077551:Micafungin