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PMID: 6946467 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 78 ·No. 8 ·1981-08-00 ·Pages 5193-6

Penno MB, Dvorchik BH, Vesell ES

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 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.

MeSH Terms
Antipyrine/blood,metabolism,urine Cytochrome P-450 Enzyme System/metabolism Female Genetic Variation Humans Kinetics Male Pregnancy Twins
Chemicals
Cytochrome P-450 Enzyme System Antipyrine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Penno M B
Dvorchik B H
Vesell E S
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.78.8.5193
Published
1981-08-00
Pages
5193-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC320370
Subset
IM
Grants
NIGMS NIH HHS · 5 R01 GM 26027 · United States
External Links
PubMed source DOI: 10.1073/pnas.78.8.5193 PMC Full Text View journal details
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