Genetic variation in rates of antipyrine metabolite formation: A study in uninduced twins

M. B. Penno, B. H. Dvorchik, E. S. Vesell

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Adult, male, unmedicated twins received anti-pyrine orally under carefully controlled environmental conditions. Relative contributions of genetic and environmental factors to 2-fold interindividual variations in rate constants for formation of the three main antipyrine metabolites were compared. Heritabilities for rate constants for formation of 4-hydroxyantipyrine, N-demethylantipyrine, and 3-hydroxymethylantipyrine were 0.88, 0.85, and 0.70, respectively. These results suggest that each molecular form of cytochrome P-450 that converts antipyrine to a different metabolite exhibits genetically controlled interindividual variations in activity. Unrelated adult male subjects whose environments were also carefully controlled exhibited highly reproducible rate constants for formation of antipyrine metabolites. Because the rate constant for metabolite formation sensitively detects certain variations in the gene product, it should be used in future pharmacogenetic studies on rates of production of multiple metabolites from a single parent drug.

Original languageEnglish (US)
Pages (from-to)5193-5196
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number8 I
StatePublished - 1981
Externally publishedYes

ASJC Scopus subject areas

  • General


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