Antipyrine metabolism in acute hepatic porphyria in relapse and remission.

Abstract

Antipyrine kinetics following a single oral dose were obtained in porphyric patients in attack and in remission and in controls. The clearance of antipyrine was significantly lower during an acute porphyric attack (median: 0.34 ml min‐1 kg‐1; range: 0.1‐0.71, P less than 0.05) than in patients in remission (median: 0.53 ml min‐1 kg‐1; range: 0.28‐0.87) or controls (median: 0.52 ml min‐1 kg‐1; range: 0.32‐ 0.93). There was a significant negative correlation between weight‐ adjusted antipyrine clearance and the urinary excretion of the porphyrin precursors, delta‐aminolaevulinic acid (r = 0.86, P less than 0.001) and porphobilinogen (r = 0.82, P less than 0.002). These data suggest that the more severe the porphyric attack, the greater the impairment of hepatic monooxygenase activity.

Limited heme synthesis in porphobilinogen deaminase‐deficient mice impairs transcriptional activation of specific cytochrome P450 genes by phenobarbital

“…Indeed, P450 activity is impaired in several heme-synthesis disorders. For example, in patients with partial genetic defects in heme synthesis enzymes, such as in acute porphyrias, the capacity to metabolize antipyrine is decreased [48].…”

Haem arginate improves hepatic oxidative metabolism in variegate porphyria.

“…Anderson et al (1976) showed that the mean plasma half-life of antipyrine was prolonged to 22 h in a group of 10 patients with porphyria in remission (eight had acute intermittent porphyria), as compared with a mean half-life of 13 h in healthy volunteers. In a group of 16 patients (14 with acute intermittent porphyria and two with variegate porphyria) the clearance of antipyrine was lower during acute attacks than during remission (Birnie et al, 1987). There was also a significant negative correlation between antipyrine clearance and the urinary excretion of porphyrin precursors.…”