Dose dependence of nicotinic acid-induced hyperbilirubinemia and its dissociation from hemolysis in Gilbert's syndrome.
The serum increments in unconjugated bilirubin and total iron were determined after intravenous administration of 5.90 mumol/kg body weight of nicotinic acid (NA) in 26 patients with Gilbert's syndrome (GS), seven patients with hemolytic anemia, and 13 healthy volunteers. The hyperbilirubinemic response, expressed as the area under time concentration curve of unconjugated bilirubin (AUCBR, milligrams per deciliter per 240 minutes) was significantly higher (P less than 0.01) in patients with GS than in controls and patients with hemolytic anemia, in whom no difference was observed. In contrast, comparable values of the hypersideremic effect (AUCFe, milligrams per deciliter per 240 minutes) were noticed among the three groups. In seven consecutive patients with GS, seven with hemolytic anemia, and four healthy volunteers, AUCBR, AUCFe, and the NA plasma half-life of the first fast slope of the curve were determined at three different doses of the drug (1.18, 2.95, and 5.90 mumol NA per kilogram body weight). A significant, dose-dependent increase in AUCBR was present in patients with GS, whereas it remained constant both in controls and in patients with hemolytic anemia. The NA plasma half-life was also significantly prolonged in GS with each of the three doses, but remained unchanged in the other two groups. In patients with GS, a linear correlation (r = 0.891, P less than 0.001) was present between AUCBR and NA plasma half-life. In contrast, the AUCFe value remained constant at the different doses used in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)
D000293:Adolescent; D000328:Adult; D000743:Anemia, Hemolytic / Q000097:blood; D001663:Bilirubin / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005878:Gilbert Disease / Q000097:blood*; D006207:Half-Life; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced*; D006933:Hyperbilirubinemia, Hereditary / Q000097:blood*; D007501:Iron / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D009525:Niacin / Q000378:metabolism / Q000494:pharmacology*
D009525:Niacin; D007501:Iron; D001663:Bilirubin