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

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 (C-max) and area under the plasma micafungin concentration-time curve (AUC(0-tau))) were similar following co-administration of micafungin and amphotericin B (day 18; C-max 19.1 mu g/mL, AUC(0-tau) 232 mu gxh/mL) compared with administration of micafungin alone (day 5; C-max 18.7 mu g/mL, AUC(0-tau) 236 mu gxh/mL), suggesting that administration of amphotericin B does not affect the PK of micafungin. The exposure to amphotericin B was similar to 30% greater following co-administration of both drugs (day 18; C-max 704 mu g/mL, AUC(0-tau) 9157 mu gxh/mL) than after administration of amphotericin B alone (day 13; C-max 621 mu g/mL, AUC(0-tau) 7023 mu gxh/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.