Fawaz F, Bonini F, Guyot M, Lagueny A M, Fessi H, Devissaguet J P
Laboratoire de Pharmacie Galénique, Faculté des Sciences Pharmaceutiques, Bordeaux, France.
Pharm Res. 1993 May;10(5):750-6. doi: 10.1023/a:1018924219540.
Following intravenous administration, the uptake of colloidal drug carriers by cells of the mononuclear phagocyte system, mainly the Kuppfer cells, may concentrate an encapsulated drug close to the liver parenchymal cells and facilitate its biliary excretion and enterohepatic circulation. To test this hypothesis indomethacin was administered (10 mg/kg) in four groups of 10 rabbits each by intravenous infusion at a constant rate over 2 hr, either in its free form (aqueous solution) or as nanocapsules prepared from preformed poly(DL-lactide). Unchanged drug was assayed in plasma of the two control (sham-operated) groups and in both plasma and bile of the two bile-cannulated groups. Pharmacokinetic analysis led to the conclusion that the uptake of nanocapsules by liver macrophages reduces the concentration of the drug by enhancing its total clearance. This enhancement was due to an increase in biliary clearance, as a result of parallel increases in bile concentration and biliary excretion of the drug. It was also demonstrated that nanocapsules enhance the enterohepatic circulation of indomethacin.
静脉给药后，单核吞噬细胞系统的细胞（主要是库普弗细胞）对胶体药物载体的摄取，可使包封的药物在肝实质细胞附近浓集，并促进其经胆汁排泄和肠肝循环。为验证这一假说，将消炎痛（10毫克/千克）以游离形式（水溶液）或由预形成的聚（DL-丙交酯）制备的纳米胶囊，通过静脉输注以恒定速率在2小时内分别给予四组兔子，每组10只。在两个对照组（假手术组）的血浆以及两个胆管插管组的血浆和胆汁中测定未变化的药物。药代动力学分析得出结论，肝巨噬细胞对纳米胶囊的摄取通过提高其总清除率而降低了药物浓度。这种提高是由于胆汁清除率增加，这是药物胆汁浓度和胆汁排泄平行增加的结果。还证明纳米胶囊增强了消炎痛的肠肝循环。
