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: P Mustajoki, J J Himberg, O Tokola, R Tenhunen
• Journal: Clinical pharmacology and therapeutics (Clin Pharmacol Ther) Vol. 51 Issue 3 Pg. 320-4 (Mar 1992) ISSN: 0009-9236 [Print] United States
• PMID: 1544288 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Heme
• 6 beta-hydroxycortisol
• Mixed Function Oxygenases
• Glucaric Acid
• Antipyrine
• Hydrocortisone

Topics

• Adult
• Aged
• Antipyrine (blood)
• Female
• Glucaric Acid (urine)
• Half-Life
• Heme (pharmacology, therapeutic use)
• Humans
• Hydrocortisone (analogs & derivatives, urine)
• Middle Aged
• Mixed Function Oxygenases (drug effects)
• Oxidation-Reduction (drug effects)
• Porphyrias (blood, therapy, urine)