Affiliation:
1. Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences and GTB Hospital (University of Delhi), Dilshad Garden, Delhi-110095, India
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) become an integral part of drug development due to their 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 evidence 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 were undertaken to evaluate the influence of environmental contaminants on drug metabolism.
Result:
Various environmental contaminants like pesticides effectively alter drug metabolism at various levels under
the influence of pharmacogenomics, which interferes with pharmacokinetics of drug metabolism. Genetic polymorphism
of phase I and phase II xenobiotic-metabolizing enzymes remarkably alters 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).
Publisher
Bentham Science Publishers Ltd.
Subject
Clinical Biochemistry,Pharmacology
Reference119 articles.
1. Dugger S.A.; Platt A.; Goldstein D.B.; Drug development in the era of precision medicine. Nat Rev Drug Discov 2018,17(3),183-196
2. Council N.R.; Toward precision medicine: building a knowledge network for biomedical research and a new taxonomy of disease 2011
3. Ravina E.; The evolution of drug discovery: from traditional medicines to modern drugs 2011
4. Debouck C.; Metcalf B.; The impact of genomics on drug discovery. Annu Rev Pharmacol Toxicol 2000,40,193-207
5. Adams M.D.; Kerlavage A.R.; Fleischmann R.D.; Fuldner R.A.; Bult C.J.; Lee N.H.; Kirkness E.F.; Weinstock K.G.; Gocayne J.D.; White O.; Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence. Nature 1995,377(6547)(Suppl.),3-174
Cited by
6 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献