Amphotericin B does not affect the pharmacokinetics of micafungin (FK463)

Abstract number: 1733_469

Undre N., Stevenson P., Wilbraham D.

Objectives: To investigate the pharmacokinetic interaction of intravenous (i.v.) micafungin (MICA) when given concomitantly with amphotericin B (AmB) following repeated administration to healthy male subjects.

Methods: This was an open-label non-randomised study. A total of 26 healthy male subjects aged between 18 and 55 years received a daily i.v. infusion of MICA (200 mg) over 1 hour for 5 days. After a 3-day washout, subjects received a daily 4-hour i.v. infusion of AmB (250 mg/kg/day) for 5 days. Subjects then received concurrent daily administration of MICA (200 mg) and AmB (250 mg/kg/day) for 5 days.

Results: Following repeated once-daily i.v. co-administration of MICA and AmB, there was no difference in the extent of systemic exposure to MICA, as measured by AUC0–24 and C_max, compared to that observed following administration of MICA alone. The geometric mean ratio (90% CI) for MICA plasma AUC0–24 and C_max after 5 days of co-administration relative to administration alone were 0.98 (0.93, 1.03) and 1.02 (0.99, 1.06), respectively. The systemic exposure to AmB increased over time by approximately 30%. This accumulation was expected based on its long half-life. These data suggest that repeated administration of MICA does not affect the pharmacokinetics of AmB.

Conclusion: There was no discernible pharmacokinetic interaction between MICA and AmB following repeated daily co-administration of both medications. Repeated i.v. doses of MICA were safe and well tolerated. Concurrent dosing with MICA and AmB was less well tolerated than either drug alone, probably owing to an accumulation of AmB towards steady state.