title: Pharmacokinetics of micafungin in healthy volunteers, volunteers with moderate liver disease, and volunteers with renal dysfunction.
abstract: Micafungin is an antifungal agent metabolized by arylsulfatase with secondary metabolism by catechol-O-methyltransferase. The objectives of this study were to estimate the pharmacokinetic parameters and plasma protein binding of micafungin in volunteers with moderate hepatic dysfunction (n = 8), volunteers with creatinine clearance < 30 mL/min (n = 9), and matched controls (n = 8 and n = 9, respectively). Single-dose micafungin pharmacokinetics were estimated using noncompartmental techniques. There was a statistically lower area under the observed micafungin concentration-time curve (AUC) from time 0 to infinity for subjects with moderate hepatic dysfunction as compared to control subjects (97.5 +/- 19 microg.h/mL vs 125.9 +/- 26.4 microg.h/mL, P = .03), although there was no difference in micafungin weight-adjusted clearance (10.9 +/- 1.7 mL/h/kg vs 9.8 +/- 1.8 mL/h/kg, P = .2). The difference in area under the concentration-time curve may be explained by the differences in body weight between subjects and controls. Renal dysfunction did not alter micafungin pharmacokinetics.
authors.affiliation: Department of Pharmacy, University of Washington, H-375 Health Sciences Center, Box 357630, Seattle, WA 98195-7630, USA. mhebert@u.washington.edu
authors.forename: Mary F
authors.initials: MF
authors.lastname: Hebert
authors.forename: Helen E
authors.initials: HE
authors.lastname: Smith
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Marbury
authors.forename: Suzanne K
authors.initials: SK
authors.lastname: Swan
authors.forename: William B
authors.initials: WB
authors.lastname: Smith
authors.forename: Robert W
authors.initials: RW
authors.lastname: Townsend
authors.forename: Donald
authors.initials: D
authors.lastname: Buell
authors.forename: James
authors.initials: J
authors.lastname: Keirns
authors.forename: Ihor
authors.initials: I
authors.lastname: Bekersky
mesh_terms: D000328:Adult; D019540:Area Under Curve; D054714:Echinocandins; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000378:metabolism*; D055666:Lipopeptides; D008074:Lipoproteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D000077551:Micafungin; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D000077551:Micafungin