HEPATIC EXCRETORY FUNCTION IN THE NEWBORN RAT

¹ Department of Pharmacology, University of Kansas Medica1 Center, Kansas City, Kansas

Hepatic disposition of sulfobromophthalein(BSP), the major metabolite of sulfobromophthalein, BSP-glutathione, and indocyanine green were studied in newborn rats of various ages. The 30-minute plasma retention of BSP was about 5-fold higher in the newborn than in adult rats and reached maturity when the rats attained one month of age. This decrease in rate of clearance in the newborn rat was accompanied by a decrease in the uptake of BSP into the liver and excretion into the small intestine. Since BSP is conjugated with glutathione in the passage through the liver, the decrease in conjugating capacity of the newborn also may play a role in the slower rate of clearance of BSP from the plasma. However, BSP-glutathione also disappeared from the plasma at a slower rate in the newborn and had a slower uptake into the liver and excretion into the intestine than in the adult rat, which suggests that a decrease in hepatic uptake and excretion probably plays a major role in the decreased rate of plasma disappearance of BSP in the newborn rat. Indocyanine green, another dye that is not biotransformed in its passage through the liver by the organic acid transport system, disappears from the plasma of the newborn rat at a slower rate than in the adult. Therefore, a decrease in the heaptic excretory function for organic acids occurs in newborn rats and may be responsible for the increased sensitivity to the toxic actions and the increased duration of action of some drugs in the newborn.