Genetic variation in rates of antipyrine metabolite formation: a study in uninduced twins.
AUTOR(ES)
Penno, M B
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=320370Documentos Relacionados
- Genetic control of the renal clearance of urate: a study of twins.
- Genetic regulation of human anti-malarial antibodies in twins.
- A study of the fertility of mothers of twins.
- Monogenic control of variations in antipyrine metabolite formation. New polymorphism of hepatic drug oxidation.
- Behavioral antecedents of accidental injuries in early childhood: a study of twins. 1971.
