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

Abstract

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. 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). 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. 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.