Journal ArticleDOI
Ethnic Differences in Drug Metabolism
TLDR
Interethnic differences in drug-metabolising capacity may be substantial, and they are sufficiently frequent to warrant attention, and new efforts are needed to adapt pharmacokinetic methods to make them suitable for population studies.Abstract:
Interethnic differences in drug-metabolising capacity may be substantial, and they are sufficiently frequent to warrant attention. Such differences may consist of different mean values of quantitative traits in separate populations, or of different frequency distributions as produced by the occurrence of genetic enzyme variants. The collection of population data requires the investigation of substantial numbers of subjects. This may be no problem if drug-metabolising enzymes occur in blood or are sufficiently stable in their tissues to allow investigation in vitro. However, if investigations require the use of probe drugs, new efforts are needed to adapt pharmacokinetic methods to make them suitable for population studies. This development of methods is further called for because genetic variants seem to be more easily detected through the assessment of particular metabolites than through the determination of pharmacokinetic parameters of the parent drug. Many studies with probe drugs comparing different populations have given results that are equivocal in terms of the nature-nurture interplay. However, a set of data with antipyrine has pointed to environmental factors as the principal determinant of differences in metabolising capacity, while data with debrisoquine have indicated monogenically controlled variation of one facet of the cytochrome P-450 system. In several instances, statistically significant differences between population means have been established by testing small numbers of subjects, numbers insufficient to establish distribution patterns that would allow the recognition of genetic polymorphism. The populations studied range from Greenlanders to South African Blacks, but most comparisons pertain to Caucasians and Orientals.read more
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The Politics of Life Itself
TL;DR: The biological existence of human beings has become political in novel ways as mentioned in this paper, and the object, target and stake of this new 'vital' politics are human life itself, which has become one of the most important sites for ethical judgements and techniques.
Journal ArticleDOI
Molecular basis of ethnic differences in drug disposition and response.
TL;DR: A better understanding of the molecular basis underlying ethnic differences in drug metabolism, transport, and response will contribute to improved individualization of drug therapy.
Journal ArticleDOI
Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations.
K Nakamura,K Nakamura,F Goto,F Goto,Wayne A. Ray,Wayne A. Ray,C B McAllister,C B McAllister,E Jacqz,E Jacqz,Grant R. Wilkinson,Grant R. Wilkinson,Robert A. Branch,Robert A. Branch +13 more
TL;DR: In this paper, the interethnic differences in debrisoquin and mephenytoin hydroxylation have been compared between normal white and Japanese subjects with the 8-hour urinary metabolic ratio and the urinary S/R enantiomeric ratio to identify extensive (EM) and poor (PM) metabolizers.
Journal ArticleDOI
Geographical/interracial differences in polymorphic drug oxidation. Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19.
TL;DR: Diazepam is partially demethylated by CYP2C19, and the high frequency of mutated alleles in Orientals is probably the reason why such populations have a slower metabolism and are treated with lower doses of diazepam than Caucasians.
Journal ArticleDOI
Pharmacogenetics of mephenytoin: a new drug hydroxylation polymorphism in man.
A Küpfer,R. Preisig +1 more
TL;DR: The co-inheritance of extensive and poor hydroxylation of mephenytoin and nirvanol, respectively, represents a new drug hydroxymation polymorphism in man.
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Journal Article
Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity.
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Genetic Control of Isoniazid Metabolism in Man
TL;DR: A patient who has signs of progressive degeneration of the spinal cord with the prospect of quadriplegia should not be deterred from timely immobilization in a light Minerva type of collar if this has a good chance of halting or reversing the disease.
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Defective N-oxidation of sparteine in man: a new pharmacogenetic defect.
TL;DR: The defective metabolism of sparteine was found to have a genetic basis and appears to be determined by two allelic genes at a single locus where nonmetabolisers are homozygous for an autosomal recessive gene.
Journal ArticleDOI
A family and population study of the genetic polymorphism of debrisoquine oxidation in a white British population.
TL;DR: A population survey of 258 unrelated white British subjects showed a polymorphism for the 4-oxidation of debrisoquine, and the alleles controlling this polymorphism appear to control the oxidation of other drugs.