Pharmacokinetic profile of micafungin when co-administered with amphotericin B in healthy male subjects

Abstract

Objective: Micafungin and amphotericin B are antifungal agents with potent activity against a broad spectrum of fungal spp., including Candida and Aspergillus. The objective of this study was to evaluate the potential pharmacokinetic (PK) interaction of the two drugs in healthy subjects.

Methods: PK were evaluated in healthy adults in an open-label, phase I clinical trial, following separate treatments with micafungin (200 mg; days 1 - 5) and conventional amphotericin B (0.25 mg/kg; days 8 - 13) alone, and following co-administration of both drugs (days 14 - 18).

Results: In 20 male subjects, systemic exposure to micafungin (measured using peak plasma micafungin concentration (Cmax) and area under the plasma micafungin concentration-time curve (AUC0-τ)) were similar following coadministration of micafungin and amphotericin B (day 18; Cmax 19.1 μg/mL, AUC0-τ 232 μg×h/mL) compared with administration of micafungin alone (day 5; Cmax 18.7 μg/mL, AUC0-τ 236 μg×h/mL), suggesting that administration of amphotericin B does not affect the PK of micafungin. The exposure to amphotericin B was ~ 30% greater following co-administration of both drugs (day 18; Cmax 704 μg/mL, AUC0-τ 9157 μg×h/mL) than after administration of amphotericin B alone (day 13; Cmax 621 μg/mL, AUC0-τ 7023 μg×h/mL). Concurrent treatment with micafungin and amphotericin B was less well tolerated than when either agent was administered alone.

Conclusions: PK and safety-related observations during co-administration of micafungin and amphotericin B were considered to be a consequence of accumulation of amphotericin B to a steady state, indicating that co-administration of the two drugs does not affect the PK of micafungin.