Effect of Environmental Exposure and Pharmacogenomics on Drug Metabolism

(E-pub Ahead of Print)

Author(s): Basu Dev Banerjee*, Ranjeet Kumar, Krishna Latha Thamineni, Harendra Shah, Gaurav Kumar Thakur, Tusha Sharma.

Journal Name: Current Drug Metabolism


Abstract:

Background: Pesticides are major xenobiotic compounds and environmental pollutants, which are able to alter drug-metabolizing enzyme as well as pharmacokinetics of drugs. Subsequent to the release of the human genome project, genetic variations (polymorphism) became an integral part of drug development due to its influence on disease susceptibility/ progression of the disease and their impact on drug absorption, distribution, metabolism of active metabolites and finally excretion of the drug. Genetic polymorphisms crucially regulate pharmacokinetics and pharmacodynamics of drugs under the influence of physiological condition, lifestyle, as well as pathological conditions collectively.

Objective: To review all the evidences concerning the effect of environmental exposure on drug metabolism with reference to pharmacogenomics.

Method: Scientific data search and review of basic, epidemiological, pharmacogenomics and pharmacokinetics studies evaluating the influence of environmental contaminant on drug metabolism.

Result: Various environmental contaminants like pesticides effectively alter drug metabolism at various levels under the influence of pharmacogenomics which interferes pharmacokinetics of the drug metabolism. Genetic polymorphism of phase I and phase II xenobiotic-metabolizing enzymes remarkably alter disease susceptibility as well as the progression of disease under the influence of various environmental contaminants at various levels.

Conclusion: Individual specific drug response may be attributed to a large variety of factors alone or in combination ranging from genetic variations (SNP, insertion, deletion, duplication etc.) to physiological setting (gender, age, body size, and ethnicity), environmental or lifestyle factors (radiation exposure, smoking, alcohol, nutrition, exposure to toxins, etc.); and pathological conditions (obesity, diabetes, liver and renal function).

Keywords: Environmental pollutants, Xenobiotics, Drug metabolism, Phase I and II metabolizing genes, Pharmacogenomics, Pesticides

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1389200221666200110153304
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