薬物肝輸送の速度論的解析

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This article consists of two parts. The first part deals with current concepts of drug transport in the liver. Hepatic uptake of bile acids and organic anions has been studied in a number of different ways including analysis of multiple indicator dilution (MID) curves, <I>in vivo</I> plasma disappearnace curves and measurements of the uptake by isolated liver cells and membrane vesicles.<BR>The advantages and disadvantages of these methods are discussed, and the principle of MID method was particularly described in detail. In spite of the diversity of methods, observations that the uptake of these compounds is saturable and that analogues compete for the uptake have generally been considered as evidence that the uptake step is carrier mediated, although the carriers for organic anions and bile acids may be different. The second part deals with the recently developed concept, that is albumin-mediated hepatic uptake of drugs. The hepatic uptake of warfarin and rose bengal was studied in rats using MID method and the isolated liver cells, respectively. The experimental data suggested the existence of serum-protein mediated uptake system. However, this protein-mediated mechanism was not only specific for albumin, but also could be seen for r-globulin
日本膜学会の論文