Genetic variation in rates of antipyrine metabolite formation: a study in uninduced twins.
- 1 August 1981
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 78 (8) , 5193-5196
- https://doi.org/10.1073/pnas.78.8.5193
Abstract
Adult, male, unmedicated twins received antipyrine 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 3 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. Each molecular form of cytochrome P-450 that converts antipyrine to a differnt metabolite seems to exhibit 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.This publication has 93 references indexed in Scilit:
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