COMPARATIVE HEPATIC TRANSPORT OF SULFOBROMOPHTHALEIN AND ITS GLUTATHIONE CONJUGATE IN RATS

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The hepatic transport of sulfobromophthalein (BSP) and its glutathione conjugate (BSP-GSH) were compared in rats by pharmacokinetic analysis in an attempt to determine the effect of conjugation on the over-all transfer of BSP from blood into bile. In the control rats, the plasma disappearance of BSP was faster than that of BSP-GSH, while the biliary excretion rate of BSP-GSH was significantly higher than that of BSP for the first 10 min. No significant difference in the total amount excreted in the bile for 4 hr was observed between two dyes. In the rats chronically intoxicated with carbon tetrachloride, typical delays were shown in both the plasma disappearance and the biliary excretion of BSP-GSH. In the control rats, the pharmacokinetic parameters, k₁₂ and k₂₃ of BSP-GSH were significantly smaller than those of BSP, while k₃₄ was significantly greater than those of BSP. In the intoxicated rats, significant decreases were observed in k₁₂, k₂₃ and k₃₄. The binding of BSP and BSP-GSH to the Y-fraction prepared from the control and intoxicated rats were studied by equilibrium dialysis. In the control rats, the number of high affinity bindings sites (n₁) of BSP-GSH was significantly smaller than that of BSP, while no significant difference was revealed in the binding constant of the high affinity binding site (K₁). In the intoxicated rats, both n₁ and K₁ of BSP-GSH were significantly smaller than those of the control rats. It was suggested that the glutathione conjugation might not play as the rate-determining step in the over-all hepatic transport of BSP.