Tin protoporphyrin prolongs the biochemical remission produced by heme arginate in acute hepatic porphyria

Abstract

Background: In acute porphyria, repletion of intrahepatic heme, with exogenously administered heme, suppresses the overproduction of δ-aminolaevulinic acid (ALA) and porphobilinogen (PBG). The effect of reducing heme breakdown has been assessed by administering tin protoporphyrin, a competitive inhibitor of heme oxygenase. Methods: The effect of tin protoporphyrin, 1 μmol/kg, and heme arginate, 3 mg/kg, individually and combined was compared with placebo in patients with an acute porphyric crisis. The treatments were given by intravenous infusion on three successive mornings. Thirty-four attacks were studied in 8 patients (9 placebo, 10 heme arginate alone, 4 tin protoporphyrin alone, and 11 combination treatments). Results: Placebo and tin protoporphyrin alone had little effect on ALA and PBG excretion. Following heme arginate alone or combined with tin protoporphyrin, there was a marked and similar suppression of both ALA and PBG excretion (P < 0.005 for each, compared with pretreatment values). However, on the 5th day after discontinuing treatment, the excretion of ALA and PBG were both lower following combination therapy than following heme arginate alone (P < 0.005 and P < 0.01, respectively). Conclusions: These findings suggest that inhibition of heme oxygenase by tin protoporphyrin prolongs the biochemical remission induced by heme arginate in the porphyric crisis.