Journal of pharmaceutical sciences
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The hepatic distribution, biliary excretion, and mass balance of liposomal amphotericin B (L-AmB) were investigated in recirculated isolated perfused rat liver. The results were compared with those from the conventional AmB formulation, amphotericin B deoxycholate (D-AmB). L-AmB was introduced as a bolus into the perfusate reservoir, at doses of 1000, 4000, and 8000 mug, to achieve therapeutically relevant concentrations. ⋯ Hepatic uptake clearance of L-AmB (CL(H,uptake)) decreased with the increase in perfusate area under the curve at each dose. The relationship between perfusate area under the curve and CL(H,uptake) was described by a parallel hepatic uptake clearance model. In conclusion, liposomal encapsulation significantly alters the hepatobiliary disposition of AmB; the ability of liposomes to sequester AmB and the dose-dependent hepatic uptake clearance may account for dose-form-dependent differences in AmB pharmacokinetics.