Disposition kinetics of amphotericin B in rats: The influence of dose

Amphotericin B (Am-B), an antifungal drug, has been used for the treatment of most disseminated fungal infections. The current therapeutic regimens for this drug are complex, at least in part as a result of limited pharmacokinetic information. In this study, we examined the disposition of Am-B as a function of dose in rats. Groups of male Sprague-Dawley rats were given Am-B by a 15-min iv infusion at three different doses. We observed no significant differences in systemic clearance among the Am-B doses studied (4.29 ± 1.42, 3.83 ± 0.29, and 3.92 ± 0.68 ml/min · kg for doses of 0.28, 0.45, and 0.84 mg/kg, respectively). Similarly, small differences were seen in volumes of distribution as a function of dose. We conclude that the disposition kinetics of Am-B were linear over the dose range studied.