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Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
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Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...
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Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases that play a pivotal role in Phase I drug metabolism by catalyzing oxidation and reduction reactions.These enzymes transform lipophilic xenobiotics into more hydrophilic metabolites, facilitating subsequent Phase II conjugation and eventual excretion. The CYP450 family is classified into families (e.g., CYP1–CYP3) and subfamilies (e.g., CYP2A, CYP2C), based on amino acid sequence homology.CYP450 isoenzymes,...
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Related Experiment Video

Updated: May 20, 2026

A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
07:52

A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy

Published on: November 7, 2017

Relationship between antioxidant enzyme genotype and activity and kidney function: a case-control study.

Amanda Crawford1, Robert G Fassett, Jeff S Coombes

  • 1University of Tasmania, School of Human Life Sciences, Launceston, Tasmania, University of Queensland, School of Medicine, St. Lucia, Australia.

Clinical Nephrology
|July 14, 2012
PubMed
Summary

Chronic kidney disease (CKD) is linked to altered antioxidant enzyme activities. Specifically, reduced plasma glutathione peroxidase (GPx) and catalase, with higher red blood cell (RBC) GPx and superoxide dismutase (SOD) activities, were observed in CKD patients.

Related Experiment Videos

Last Updated: May 20, 2026

A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
07:52

A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy

Published on: November 7, 2017

Area of Science:

  • Biochemistry
  • Genetics
  • Nephrology

Background:

  • Oxidative stress is a key factor in chronic kidney disease (CKD) progression.
  • The association between antioxidant enzyme single nucleotide polymorphisms (SNPs) and CKD remains under-investigated.
  • This study examines SNPs in superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase in relation to CKD.

Purpose of the Study:

  • To compare antioxidant genotypes and enzyme activities between CKD patients and healthy controls.
  • To investigate the relationship between these genetic variations, enzyme activities, and kidney function (eGFR).

Main Methods:

  • Genotyping for GPx, SOD, and catalase SNPs in 230 CKD patients and 224 controls.
  • Measurement of plasma and red blood cell (RBC) enzyme activities (GPx, SOD, catalase).
  • Assessment of estimated glomerular filtration rate (eGFR) to evaluate kidney function.

Main Results:

  • CKD patients showed a higher prevalence of the GPx Leu/Leu genotype compared to controls (p=0.054).
  • Significantly lower plasma GPx and RBC catalase activities were found in CKD patients.
  • Conversely, RBC GPx and RBC SOD activities were significantly higher in CKD patients (p < 0.001).

Conclusions:

  • CKD is associated with distinct alterations in antioxidant enzyme activities, including reduced plasma GPx and catalase, and enhanced RBC GPx and SOD.
  • While overall genotype frequencies were similar, the GPx Leu/Leu genotype was linked to lower eGFR in CKD patients.
  • These findings highlight the role of antioxidant enzyme activity modulation in CKD pathogenesis.