Plasma clearance of nicotinic acid and rifamycin-SV, and their interaction in Gilbert's syndrome: application of a compartmental model.

The bicompartmental kinetics of nicotinic acid (NA) and rifamycin-SV (R-SV)--2 organic anions that probably share a common hepatic uptake mechanism--were studied in 7 cases of Gilbert's syndrome (GS) and in 7 healthy controls matched for sex and age. In GS the NA and R-SV uptake constants (K21) were significantly decreased. In GS patients, simultaneous loads of NA and R-SV, the latter at increasing doses, produced: 1) a progressive lowering only of R-SV K21; and 2) an increase in R-SV hepatic plasma reflux (K12). Changes in biliary excretion ( Kee ) and hepatocellular pool (Ke) of both NA and R-SV probably depend on the rates of uptake and reflux constants of the two anions. The study of the parameters of compartmental kinetics of NA and R-SV confirms that the two organic anions, which have different metabolic routes and/or a different affinity for intracellular carriers, share common uptake mechanisms.