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The effects of industrial lead poisoning on cytochrome P450 mediated phenazone (antipyrine) hydroxylation

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Summary

In a group of ten male adults admitted to hospital with clinical symptoms of lead exposure, phenazone elimination rates, blood δ-amino-laevulinic acid dehydratase (ALA.D) activity, blood lead levels and haemoglobin were measured. Investigations were carried out before, immediately after and again at least 12 weeks after cessation of CaEDTA (sodium calcium edetate) chelation therapy. Following chelation, phenazone elimination rates were increased as assessed by a decrease in half life and increase in clearance. This was significant, both immediately after and 12 weeks after cessation of chelation therapy. The change in rate of phenazone metabolism was associated with improved clinical status, with lowered blood lead levels and raised haemoglobin and ALA.D activity. The results of the study suggest that the depression in phenazone elimination in lead intoxication is possibly due to depressed hepatic cytochrome P450 levels.

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Meredith, P.A., Campbell, B.C., Moore, M.R. et al. The effects of industrial lead poisoning on cytochrome P450 mediated phenazone (antipyrine) hydroxylation. Eur J Clin Pharmacol 12, 235–239 (1977). https://doi.org/10.1007/BF00609867

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  • DOI: https://doi.org/10.1007/BF00609867

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