Related Experiment Videos
Theophylline metabolism: variation and genetics.
Clinical Pharmacology and Therapeutics
|February 1, 1984
Summary
Genetic factors play a smaller role in theophylline metabolism than previously thought, though a rare gene may influence it. Environmental factors like smoking and sex also impact drug metabolism rates.
Area of Science:
- Pharmacogenetics
- Drug Metabolism
- Human Genetics
Background:
- Theophylline metabolism exhibits inter-individual variability.
- Twin studies are crucial for dissecting genetic and environmental influences on drug metabolism.
Purpose of the Study:
- To investigate the contribution of genetic and environmental factors to theophylline metabolism variability.
- To compare theophylline pharmacokinetics and metabolite excretion in monozygotic (MZ) and dizygotic (DZ) twins.
Main Methods:
- Kinetic study of theophylline metabolism in 54 healthy adults (MZ twins, DZ twins, singletons).
- Assessed elimination rate constant, clearance (Cl), half-life (t1/2), apparent volume of distribution.
- Measured urinary excretion of theophylline and its major metabolites (1-methyluric acid, 3-methyl-xanthine, 1,3-dimethyluric acid).
Main Results:
- Smokers and men exhibited significantly higher theophylline elimination rates than nonsmokers and women.
- While MZ twins showed closer resemblance in kinetic parameters than DZ twins, differences were not statistically significant for most measures.
- Heritability estimates indicated a smaller genetic contribution to theophylline metabolism variation compared to other studied drugs.
Conclusions:
- Environmental factors, particularly smoking and sex, significantly influence theophylline metabolism.
- Genetic factors appear to contribute less to theophylline metabolism variability than suggested by previous twin studies for other drugs.
- A rare major gene potentially retarding theophylline metabolism cannot be excluded, as suggested by a family with slow clearance (Cl).