title: Studies in porphyria. V. Drug oxidation rates in hereditary hepatic porphyria.
abstract: The mean plasma half-life (T1/2) of antipyrine was prolonged (21.69 +/- 1.92 hr) in a group of 10 patients with hereditary hepatic porphyria, 8 of whom had acute intermittent porphyria (AIP) confirmed by decreased erythrocyte uroporphyrinogen-1-synthetase (URO-S) activities and 2 of whom had mixed hepatic porphyria, in comparison to the mean of 20 normal control subjects (12.65 +/- 0.86 hr, p less than 0.01). Antipyrine T1/2 was especially prolonged in patients with a history of more severe symptoms, but there was no correlation with the degree of elevation in urinary excretion of the porphyrin precursors delta-aminolevulinic acid (ALA) and porphobilinogen (PBG). In 7 completely latent carriers of the AIP gene defect who had normal urinary ALA and PBG levels, the elimination rates of antipyrine from plasma were entirely normal. Phenylbutazone T1/2s were normal in 10 porphyric patients tested. These results demonstrate that the cytochrome P-450-dependent enzyme system for oxidizing antipyrine, but not that for phenylbutazone, is impaired in some AIP individuals in whom the gene defect for the disorder is clinically expressed and that this impairment may be related to the severity of the disease. The partial decrease in URO-S activity characteristic of AIP does not result in a profound or generalized decrease in hepatic cytochrome P-450 function, however, even when there is sufficient derangement in the hepatic heme biosynthetic pathway to lead to excessive excretion of chemical intermediates in the pathway.
mesh_terms: D000328:Adult; D000622:Aminolevulinic Acid / Q000652:urine; D000983:Antipyrine / Q000097:blood*; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D006207:Half-Life; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000097:blood; D007700:Kinetics; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010653:Phenylbutazone / Q000097:blood*; D011162:Porphobilinogen / Q000652:urine; D011164:Porphyrias / Q000235:genetics / Q000378:metabolism*
chemical_list: D011162:Porphobilinogen; D000622:Aminolevulinic Acid; D011163:Hydroxymethylbilane Synthase; D010653:Phenylbutazone; D000983:Antipyrine