title: Rapid normalization of antipyrine oxidation by heme in variegate porphyria.
abstract: Effects of heme on hepatic xenobiotic drug metabolism were investigated in eight subjects with variegate porphyria. A single infusion of heme arginate (3 mg/kg heme) reversed rapidly the prolonged mean elimination half-life of antipyrine from 27.2 to 12.7 hours (p less than 0.001) and increased total clearance from 0.23 to 0.44 ml/min/kg (p less than 0.001). Excretion of 6 beta-hydroxycortisol and D-glucaric acid increased significantly during heme infusion. Excretion of urinary porphyrin precursors increased during the antipyrine test but was normalized by heme. It is concluded that in variegate porphyria a partial block in heme biosynthesis results in subnormal capacity of P450-associated monooxygenases, but this is easily normalized by exogenous heme.
authors.affiliation: Third Department of Medicine, University of Helsinki, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Mustajoki
authors.forename: J J
authors.initials: JJ
authors.lastname: Himberg
authors.forename: O
authors.initials: O
authors.lastname: Tokola
authors.forename: R
authors.initials: R
authors.lastname: Tenhunen
mesh_terms: D000328:Adult; D000368:Aged; D000983:Antipyrine / Q000097:blood*; D005260:Female; D005937:Glucaric Acid / Q000652:urine; D006207:Half-Life; D006418:Heme / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000187:drug effects*; D010084:Oxidation-Reduction / Q000187:drug effects; D011164:Porphyrias / Q000097:blood / Q000628:therapy* / Q000652:urine
chemical_list: D006418:Heme; C001380:6 beta-hydroxycortisol; D006899:Mixed Function Oxygenases; D005937:Glucaric Acid; D000983:Antipyrine; D006854:Hydrocortisone