Pharmacokinetic aspects of sulfobromophthalein transport in chronically carbon tetrachlorideintoxicated rats

Abstract

In order to elucidate the factors affecting the hepatic transport of sulfobromophthalein (BSP) in a pathological condition, the kinetics of the disappearance of BSP from the blood and appearance in the bile were studied in rats chronically intoxicated with carbon tetrachlorde, and the importance of factors that might affect the kinetics, i.e. binding activites of plasma and hepatic cytoplasmic proteins, and glutathione S-transferase activity of Y-fraction, was examined. During chronic intoxication, although plasma protein albumin concentration decreased, no qualitative difference was shown in the high affinity binding site ( K 1). A significant decrease was shown in the cytoplasmic protein concentration for the Y- and Z-fractions in intoxicated rats; no significant difference was observed in the number of binding sites for both fractions, but their binding constants decreased. Glutathione S-transferase activity and glutathione (GSH) content were not altered, although a decrease in conjugating activity per rat was expected. The time course for the plasma disappearance and biliary excretion of BSP showed a remarkable delay after CCl 4 intoxication, while no difference was shown in the bile flow rate. It was concluded that hepatic blood flow might play a primary ro)e in the initial plasma disappearance of BSP and that the decrease in the Y-fraetion binding activity might explain the decrease in BSP uptake rate into the liver which was observed in intoxicated rats.