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KMID : 0369819920220010011
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Jorunal of Korean Pharmaceutical Sciences
1992 Volume.22 No. 1 p.11 ~ p.21
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Kinetic Analysis of the Hepatic Transport of Organic Anions : Role of Intracellular Cytoskeleton
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정연복/Chung YB
한건/육동연/Han K/Yuk DY
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Abstract
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The effects of colchicine on the plasma elimination and biliary excretion of various organic anions in rats were examined. Elimination of indocyanine green (ICG) or rose bengal (RB) from plasma was significantly delayed when rats were treated with colchicine (3 mg/kg body weight) 3 hr prior to the administration of the dye. On the other hand, disappearance of sulfobromophthalein (BSP) or bromophenol blue (BPB) from plasma was not influenced by colchicine. The plasma disappearance and biliary excretion of organic anions were kinetically analyzed based on a compartment model, in which the deep compartment and the unknown disposition are incorporated. The transfer rate constants of ICG or RB, k23 (from the liver to the deep compartment) and k3B (from the deep compartment to the bile), were decreased by colchicine, but those of BSP or BPB were not changed. A mechanism for the decrease in the k23 and k3B values for ICG and RB might be explained by a inhibition of colchicine to the intracellular cytoskeleton. The hepatocellular distribution of RB or BPB was then determined. BPB mainly distributed to the cytosolic fraction, but RB distributed to each hepatocyte organelle. Taken together. it was suggested that ICG or RB is transported through hepatocytes into bile with the aid of the cytoskeleton, whereas BSP or BPB is handled by hepatocytes in a different way.
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KEYWORD
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Organic anions, biliary excretion, indocyanine green, rose bengal, colchicine, sulfobromophthalein, bromophenol blue, cytoskeleton, hepatocyte
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