Effect of Haem Arginate Therapy on Porphyrin Metabolism and Mixed Function Oxygenase Activity in Acute Hepatic Porphyria

Haem arginate improves hepatic oxidative metabolism in variegate porphyria.

“…The results of the present study indicate an even greater improvement in drug metabolism. Thus, antipyrine clearance increased by about five-fold, whereas it was less than doubled in the study of Herrick et al (1987). They showed clear improvement in antipyrine elimination even after the first haem arginate infusion whereas we investigated the effects of a full treatment course of haem (i.e.…”

“…three to four infusions). In the symptomatic stage of the disease it is necessary to give antipyrine intravenously (as Herrick et al, 1987 did) due to changes in gastrointestinal motility described during acute attacks of porphyria.…”

“…There was also a significant negative correlation between antipyrine clearance and the urinary excretion of porphyrin precursors. Herrick et al (1987) demonstrated that haem arginate improved hepatic mixed function oxygenase activity and suppressed the overproduction of porphyrin precursors during acute attacks in patients with acute intermittent porphyria. The purpose of this study was to investigate drug metabolism in variegate porphyria, where the enzyme defect is more distal than in acute intermittent porphyria.…”

“…The pharmacokinetics of intravenously administered haem arginate have been reported both in healthy volunteers and porphyric patients . Haem arginate normnalizes the excessive urinary excretion of porphobilinogen and 8-aminolaevulinic acid in patients with acute intermittent porphyria, and the high concentrations of proto-and coproporphyrins in patients with variegate porphyria Korda6 & MartAsek, 1986; Devars du Mayne et al, 1986;Herrick et al, 1987).…”

Heme-Regulated Inhibitor (HRI) eIF2α Kinase and the Heme-Regulated Turnover of Cytochromes P450 and Other Hepatic Proteins

“…Such enhanced P450 degradation may contribute to the impairment of P450-dependent drug clearance in patients with acute hepatic porphyria. [111][112][113] Thus, the finding that heme depletion not only shuts off de novo synthesis of P450s but also enhances their degradation reveals an exquisite heme control of hepatic P450 turnover that is conceivably mediated by hepatic HRI. Such regulation of hepatic P450 content through prosthetic function and altered proteolytic turnover upon acute hepatic heme depletion, indicates a concerted cellular effort to conserve heme at the expense of P450s, the major consumers of hepatic heme.…”