Sulfobromophthalein (BSP) clearance hasproved a sensitive index of hepatic function. Although dosage, sampling intervals and techniques of measurement have been modified (1)(2)(3)(4), the procedure remains essentially as originally described (5, 6). Basically it conisists of the intravenous injectioni of a stanidard amiiount of BSP and determination of residual BSP in the plasma from blood samples collected at prescriled intervals.Since clearanice of BSP is (lecreased 1)oth in hlepatocellular dysfunction anid biliary obstruction, its determination is of limited usefulness in differentiating these two conditions. Recent studies, however, have shown that BSP is conjugated in the liver and excreted primarily as conjugates into the bile and to a lesser extent into the urine (7-11). Chemical analysis indicates that the dye is conjugated witlh cysteine and possibly with the peptide, glutatlhione (12). These metabolites are colorimetrically indistinguishable from free BSP. The demonstration that sulfobromophthalein is conjugated by the liver suggests the following possibilities: 1) where uptake or hepatic conjugation of BSP is impaired due to parenchymal dysfunction, the circulating dye should remain in the unconjugated form; 2) in biliary obstruction, where conjugation of the dye proceeds normally but secretion from the liver is impaired, increasing amounts of conjugated dye should appear in the blood. If such is true, the determination of the metabolized BSP, in addition to total BSP, in serum miglht serve to distinguish impairment of uptake or conjugation from intrahepatic or extrahepatic biliary obstructioln.In this study the levels of free and conijugated * Supported by a grant (A-2455) from the National Institutes of Health, United States Public Health Service, Bethesda, Md. BSP wvere investigated in sera and urine from nornmal subjects and patients with hepatic disease. SUBJECTS AND METHODSThe 87 subjects selected for study consisted of 17 patients with normal liver functioni, 10 patients in whom liver funictioni tests and clinical work-up (including liver biopsy wheni feasible) indicated viral hepatitis, 33 patients with portal cirrhosis and varying degrees of hepatic decompenisationi, 10 patients with extrahepatic obstruction as indicated by liver function studies and coInfirmed by surgical explorationi, anid 17 patients initially with niormal liver functioni who were given methyltestosterone (67 mg. per day) for 14 days.The following liver function tests were carried out in each group: total serum protein and albumin (13); alkaline phosphatase (14) (upper limit of normal in our laboratory is 8 units) ; one minute and total bilirubin (15) and 45 minute BSP retentioni (16). In addition, serum glutamic oxalacetic transaminase levels (17) were determined in the subjects treated with methyltestosterone.The circulating level of BSP metabolites was determined in fasting subjects as follows. Commercial BSP (5 mg. per Kg. body weight) was injected intravenously. Blood was drawn from the opposite arm at specific int...

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With the use of a standard dose of sulfobromophthalein sodium (BSP), the metabolism of this substance was studied in a group of full-term and premature infants (normal, hypoxic, and hyperbilirubinemic). Elevated total BSP and BSP conjugate at birth in normal full-term and premature infants approached normal adult levels toward the end of the third week of life. There was no significant difference between the rate of decrease of total or conjugated BSP in the full-term and premature infant. During the first 20 days of life the decrease in total BSP levels proceeded at a faster rate than the decline in BSP conjugate in both normal groups. The mean concentrations of total BSP and BSP conjugate were higher in infants with hypoxia, hyperbilirubinemia, and hemolytic disease of the newborn than in normal infants, but the difference was not statistically significant.