title: Impact of plasma exchange on pharmacokinetic disposition of micafungin.
abstract: Change in the pharmacokinetic disposition of an antifungal agent micafungin (MCFG) by 8-hour plasma exchange (PE) with 3200 mL replacement was examined in a stem cell transplant recipient. On pharmacokinetic analysis of the time course of the serum concentrations of MCFG, it was determined that PE shortened the elimination half-life of MCFG from 16.5 hours to 6.3 hours. Total clearance (CL(tot)) was increased from 0.366 L/h to 0.932 L/h by PE. PE-dependent clearance (CL(pe)) accounted for approximately two-thirds of CL(tot), and PE was found to contribute to the removal of nearly 40% of the total body store of MCFG. It was confirmed that a significant amount of MCFG was excluded into apheresed plasma waste. In addition, adsorption of MCFG onto plasma-separating membrane was strongly suggested, because the CL(pe) exceeded the rate of plasma apheresis and MCFG concentrations in apheresed plasma were lower than those in circulating blood collected at the same time. The marked elimination of MCFG during PE can be explained by its low volume of distribution and high affinity for serum proteins. Judging from these findings as well as those of other reports, MCFG can be considered one of the drugs most susceptible to removal by PE. Our findings suggest that an increment in the regular dose of MCFG would be required at the next administration after PE.
authors.affiliation: Laboratory of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Osaka Ohtani University, Nishikiori-kita, Tondabayashi, 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: Takao
authors.initials: T
authors.lastname: Saotome
authors.forename: Tetsu
authors.initials: T
authors.lastname: Hamamoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Eguchi
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: Akira
authors.initials: A
authors.lastname: Yamaji
mesh_terms: D000935:Antifungal Agents / Q000493:pharmacokinetics*; D054714:Echinocandins / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D055666:Lipopeptides / Q000493:pharmacokinetics*; D000077551:Micafungin; D008875:Middle Aged; D010951:Plasma Exchange; D011485:Protein Binding; D033581:Stem Cell Transplantation / Q000379:methods; D014018:Tissue Distribution
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077551:Micafungin