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Rapid normalization of antipyrine oxidation by heme in variegate porphyria
Author(s) -
Mustajoki Pertti,
Himberg JaakkoJuhani,
Tokola Olavi,
Tenhunen Raimo
Publication year - 1992
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1992.28
Subject(s) - porphyria , heme , chemistry , porphyrin , medicine , endocrinology , excretion , monooxygenase , metabolism , pharmacology , cytochrome p450 , biochemistry , enzyme
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 < 0.001) and increased total clearance from 0.23 to 0.44 ml/min/kg ( p < 0.001). Excretion of 6β‐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. Clinical Pharmacology and Therapeutics (1992) 51, 320–324; doi: 10.1038/clpt.1992.28