Pharmacokinetics of Micafungin in Adult Patients with Invasive Candidiasis and Candidemia

摘要

Micafungin is an efficacious and well-tolerated echinocandin with in vitro and in vivo activity against a broad range of Candida species. The objective of this randomized, double-blind study was to examine the pharmacokinetic parameters of micafungin and its metabolites in a subset of adult patients with invasive candidiasis or candidemia. The study was conducted at 27 sites in four countries, including eight in Europe. Micafungin 100 mg/day or liposomal amphotericin B 3 mg/kg/day were administered once daily as a 1-hour infusion in a blinded manner. The minimum duration of therapy was 14 days. To define plasma analyte (micafungin and metabolites) concentration-time profiles, serial blood samples were collected after the first dose (Day 1), and at the end of therapy (EOT). For patients who received treatment for longer than 2 weeks, an additional profile was obtained during Week 2. To determine plasma trough analyte concentrations, blood samples were collected immediately prior to dosing on Day 2, Week 2, and EOT. In 20 evaluable, micafungin-treated patients, plasma micafungin concentrations peaked at completion of the 1-hour infusion and then declined biexponentially. Plasma concentrations of the micafungin metabolites (M-1, M-2, and M-5) remained low (<1 μg/mL) throughout the study. The mean half-life and clearance of micafungin were largely unchanged with repeated dosing up to 28 days, and no evidence of micafungin accumulation was observed. These data provide further support for the predictability of micafungin pharmacokinetics in adult patients with invasive candidiasis and candidemia.