Pharmacokinetics of micafungin in healthy volunteers, volunteers with moderate liver disease, and volunteers with renal dysfunction.
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.
Hebert
Mary F
MF
Department of Pharmacy, University of Washington, H-375 Health Sciences Center, Box 357630, Seattle, WA 98195-7630, USA. mhebert@u.washington.edu
Smith
Helen E
HE
Marbury
Thomas C
TC
Swan
Suzanne K
SK
Smith
William B
WB
Townsend
Robert W
RW
Buell
Donald
D
Keirns
James
J
Bekersky
Ihor
I
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*
D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D000077551:Micafungin