title: Pharmacokinetics of micafungin in subjects with severe hepatic dysfunction.
abstract: Micafungin is an echinocandin with potent activity against a broad range of fungal species, including Candida species. The pharmacokinetic and safety profiles of micafungin have been evaluated in individuals with mild-to-moderate hepatic dysfunction, but not in individuals with severe hepatic dysfunction. Therefore, the present study assessed the pharmacokinetics and safety of a single 100 mg dose of micafungin in healthy subjects (n = 8) and subjects with severe hepatic dysfunction (n = 8). Mean maximum plasma concentration of micafungin and mean area under the plasma micafungin concentration-time curve extrapolated to infinity were lower in subjects with severe hepatic dysfunction (7.3 ± 2.4 µg/mL and 100.1 ± 34.5 h·μg/mL, respectively) than in subjects with normal hepatic function (10.3 ± 2.5 µg/mL and 142.4 ± 28.9 h·μg/mL, respectively). Mean clearance was higher in subjects with severe hepatic dysfunction (1,098 ± 347 mL/h) than in subjects with normal hepatic function (728 ± 149 mL/h). Concentrations of albumin in subjects with severe hepatic dysfunction were lower. Assessments of micafungin plasma protein binding suggested that the higher clearance in subjects with severe hepatic dysfunction may be due to higher unbound concentrations. However, the magnitude of the differences was not considered clinically meaningful and is comparable with exposures reported elsewhere for a 100-mg dose in patients treated for invasive candidiasis. Thus, dose adjustment in subjects with severe hepatic dysfunction is not warranted. Micafungin was well tolerated in all subjects throughout the study.
authors.affiliation: Astellas Pharma Europe Ltd, 2000 Hillswood Drive, Chertsey, KT16 0RS, UK, nas.undre@astellas.com.
authors.forename: Nasrullah
authors.initials: N
authors.lastname: Undre
authors.forename: Benjamin
authors.initials: B
authors.lastname: Pretorius
authors.forename: Paul
authors.initials: P
authors.lastname: Stevenson
mesh_terms: D019540:Area Under Curve; D016022:Case-Control Studies; D054714:Echinocandins / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D055666:Lipopeptides / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D000077551:Micafungin; D008875:Middle Aged
chemical_list: D054714:Echinocandins; D055666:Lipopeptides; D000077551:Micafungin