Abnormal hepatic uptake of low doses of sulfobromophthalein in Gilbert's syndrome: the role of reduced affinity of the plasma membrane carrier of organic anions.
The plasma disappearance rate of sulfobromophthalein (VBSP; mumol/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 mumol/kg) of the dye. Plasma disappearance rate was significantly reduced in Gilbert's syndrome patients after administration of 0.59 mumol sulfobromophthalein/kg (0.119 +/- 0.016 vs. 0.146 +/- 0.018 mumol/kg/min; mean +/- S.D.; p less than 0.001), whereas no difference was found with the higher dose (0.754 +/- 0.040 vs. 0.767 +/- 0.072 mumol/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 mumol sulfobromophthalein (0.060 +/- 0.005 mumol/kg/min vs. 0.077 +/- 0.07 mumol/kg/min and 0.480 +/- 0.012 mumol/kg/min vs. 0.591 +/- 0.015 mumol/kg/min, respectively; p less than 0.01). Competition studies with combined administration of sulfobromophthalein (0.59 mumol/kg) and different doses of rifamycin SV (0.59, 1.47 and 2.95 mumol/kg) showed a significant (p less than 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 mumol/kg. The apparent affinity (Km) of the hepatic transport was higher in Gilbert's syndrome patients than in control subjects (3.61 +/- 0.37 mumol sulfobromophthalein/kg vs. 2.76 +/- 0.29 mumol sulfobromophthalein/kg, mean +/- S.D.; p less than 0.01), whereas no difference was found in Vmax (0.95 +/- 0.11 mumol sulfobromophthalein/kg vs. 0.93 +/- 0.10 mumol sulfobromophthalein/kg/min, mean +/- S.D.; N.S.).(ABSTRACT TRUNCATED AT 250 WORDS)
Gentile
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Istituto Medicina Generale e Metodologia Clinica, I Facoltá di Medicina, Universitá di Napoli, Italy.
Persico
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Tiribelli
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D000293:Adolescent; D000328:Adult; D000838:Anions / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005878:Gilbert Disease / Q000378:metabolism*; D006801:Humans; D006933:Hyperbilirubinemia, Hereditary / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D012016:Reference Values; D013448:Sulfobromophthalein / Q000493:pharmacokinetics*
D000838:Anions; D002352:Carrier Proteins; D013448:Sulfobromophthalein