Impaired hepatic disposition of sulfobromophthalein sodium in neonatal guinea pigs: nature of the defect.

Abstract

Abstract Hepatic disposition of sulfobromophthalein sodium (BSP) was studied in newborn guinea pigs from the second to the sixteenth day of life after intravenous administration of doses of unconjugated and conjugated dye sufficient to achieve maximal rates of dye excretion into bile. Neonatal guinea pigs injected with unconjugated BSP showed a marked reduction in the maximal rate of dye excretion into bile when compared to adult animals given comparable weight-adjusted doses of unconjugated BSP. A minimal estimate of hepatic uptake of unconjugated dye revealed uptake to be comparable in neonatal and adult animals and significantly greater than maximal rates of dye excretion into bile; hepatic uptake did not limit hepatic disposition of unconjugated dye. Analysis of BSP compounds in the bile of these animals revealed that both unconjugated and conjugated dye appeared in decreased amounts. With aging, injected unconjugated dye was excreted at progressively more rapid rates. This was accounted for by almost proportionate increases in output of both unconjugated and conjugated forms of the dye. Quantitatively, increased output of unconjugated BSP into bile was the major factor accounting for improvement in dye excretion in neonatal animals infused with unconjugated BSP. By contrast, neonatal animals from the second day of life excreted injected conjugated BSP into bile as readily as adult guinea pigs. The studies are interpreted as indicating that impaired hepatic disposition of injected unconjugated BSP in the neonatal guinea pig is due to a combination of decreased transport of unconjugated dye from liver cells into bile, and decreased conjugation of BSP.