Impaired plasma clearance of nicotinic acid and rifamycin-SV in Gilbert's syndrome: evidence of a functional heterogeneity.

Patients with Gilbert's syndrome (GS) have impaired clearance by the liver of some organic anions. We looked for possible differences in hepatic clearance of nicotinic acid (NA) and rifamycin-SV (R-SV) among GS patients, and examined the effect produced by these anions on the plasma levels of unconjugated bilirubin (UCB). Two subgroups of GS patients, GS1 and GS2, were differentiated according to their ability to handle R-SV and NA. Compared with a control group, the alteration of the half-life both of NA and R-SV was less marked in GS1 than in GS2. UCB plasma concentration after NA and R-SV loading was more greatly increased in GS2 than in GS1 patients. In addition, a striking correlation was found in all subjects studied between UCB and the half-life of NA and R-SV. These related alterations of plasma UCB and plasma half-life or organic anions suggests a common defect of hepatic uptake. It is hypothesized that this defect is located at the level of a hepatic plasma membrane carrier.