Studies on amphotericin B pharmacokinetics. (2). Analysis of the elimination process.:Analysis of the Elimination Process

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Pharmacokinetics of amphotericin B (AMPH) were studied in rat and human. The concentration of AMPH was determined by high-performance liquid chromatography.In animal experiments, AMPH syrup (96mg/kg, p. o.) or an AMPH injectable solution (0.5mg/kg, i. v.) was administered to rats and their urine and feces were collected for ten days thereafter. The cumulative recovery of orally administered AMPH was 0.04% (6.31μg) in urine and 88.9% in feces, and the recovery of intravenously administered AMPH was 6.45% (5.48μg) in urine and 31.07% in feces. This result suggested that a considerable amount of AMPH in blood was excreted into bile, because the amount of AMPH eliminated into urine after oral administration was almost equal to that following intravenous administration.In human experiments, bile and liver samples were obtained from patients with liver disease after liver resection. AMPH syrup (4, 800mg/day, p. o.) was administered 20 hours before the liver resection. The concentrations of AMPH in both bile and liver tissue were higher than the concentration in serum.It therefore appears that a considerable amount of AMPH can be absorbed from the digestive tract after oral administration. The bioavailability of orally given AMPH has been thought to be low, but from these results we believe that the bioavailability is much higher and should be re-evaluated.
日本医真菌学会の論文