Rapid normalization of antipyrine oxidation by heme in variegate porphyria

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.