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Abstract

The plasma disappearance rate of sulfobromophthalein (VBSP; μmol/kg/min) was measured in 15 Gilbert's syndrome patients and 12 control subjects after intravenous injection of two different doses (0.59 and 5.90 μmol/kg) of the dye. Plasma disappearance rate was significantly reduced in Gilbert's syndrome patients after administration of 0.59 μmol sulfobromophthalein/kg (0.119 ± 0.016 vs. 0.146 ± 0.018 μmol/kg/min; mean ± S.D.; p < 0.001), whereas no difference was found with the higher dose (0.754 ± 0.040 vs. 0.767 ± 0.072 μmol/kg/min). Significant reduction was also found after administration to four Gilbert's syndrome patients and four control subjects of 0.29 and 2.95 μmol sulfobromophthalein (0.060 ± 0.005 μmol/kg/min vs. 0.077 ± 0.07 μmol/kg/min and 0.480 ± 0.012 μmol/kg/min vs. 0.591 ± 0.015 μmol/kg/min, respectively; p < 0.01). Competition studies with combined administration of sulfobromophthalein (0.59 μmol/kg) and different doses of rifamycin SV (0.59, 1.47 and 2.95 μmol/kg) showed a significant (p < 0.001) reduction in plasma disappearance rate in Gilbert's syndrome patients but not in controls. The rifamycin SV dose at which a 50% inhibition in plasma disappearance rate was observed was 0.8 μmol/kg. The apparent affinity (Km) of the hepatic transport was higher in Gilbert's syndrome patients than in control subjects (3.61 ± 0.37 μmol sulfobromophthalein/kg vs. 2.76 ± 0.29 μmol sulfobromophthalein/kg, mean ± S.D.; p < 0.01), whereas no difference was found in Vmax (0.95 ± 0.11 μmol sulfobromophthalein/kg vs. 0.93 ± 0.10 μmol sulfobromophthalein/kg/min, mean ± S.D.; N.S.). We conclude that a defective sulfobromophthalein hepatic transport is present in Gilbert's syndrome, and it may be revealed by lowering the does of the dye. The data sugest that the defect in Gilbert's syndrome is an impaired affinity for sulfobromophthalein of one or more of the putative transport proteins in the basolateral plasma membrane of the hepatocyte. (HEPATOLOGY 1990;12:213–217).