Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance

Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance

The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...

Principles of Pharmacogenetics: Types of Genetic Variants

Principles of Pharmacogenetics: Types of Genetic Variants

The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...

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

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...

Pharmacogenetics of Drug Metabolism: Overview

Pharmacogenetics of Drug Metabolism: Overview

Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

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,...

Drug toxicity: Idiosyncratic Reactions

Drug toxicity: Idiosyncratic Reactions

Idiosyncratic drug reactions represent abnormal chemical responses that vary significantly among individuals, ranging from extreme sensitivity to low doses to insensitivity to high doses. These reactions often occur due to the drug's covalent binding with serum proteins, forming a foreign hapten that triggers an immunotoxicological response. The variability in drug reactions has a strong pharmacogenetic foundation, with genetic differences crucial in how individuals metabolize drugs. For...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

The impact of pectin supplementation on systemic inflammation pathways, gut microbiome, and metabolic health in patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A study protocol for a randomised controlled trial.

PloS one·2026

Same author

Single-Cell Transcriptomic Analysis Reveals γδ T-Cell Infiltration and Presence of Immune Regulatory Molecules in Biliary Tract Cancer Microenvironment.

American journal of clinical oncology·2026

Same author

Burden of non-cancer comorbidities and mortality in chronic pancreatitis: a retrospective cohort study.

BMJ open gastroenterology·2026

Same author

Integrated multi-omics identifies distinct macrophage alterations during progression of metabolic dysfunction-associated steatohepatitis.

Nature genetics·2026

Same author

HLA-B44 Alleles and HLA-DQA103:01 as Genetic Risk Factors for Drug-Induced Liver Injury due to Fluoroquinolones.

Liver international : official journal of the International Association for the Study of the Liver·2026

Same author

TeloNet is born: why all specialities need to be aware of telomere biology disorders.

Frontiers in medicine·2026

Search research articles

Related Experiment Video

Updated: Jul 7, 2026

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures

Published on: March 28, 2017

Upstream and coding region CYP2C9 polymorphisms: correlation with warfarin dose and metabolism.

Barry P King¹, Tayyaba I Khan, Guruprasad P Aithal

¹School of Clinical and Laboratory Sciences, University of Newcastle upon Tyne, Medical School, Newcastle upon Tyne, UK.

Pharmacogenetics

|December 21, 2004

Summary

The primary factor influencing warfarin dose in UK Caucasians is the CYP2C9*2 and CYP2C9*3 genetic variants. Other upstream CYP2C9 polymorphisms do not significantly impact warfarin dose requirements or metabolism.

More Related Videos

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene

Published on: April 1, 2019

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform

Published on: May 10, 2024

Related Experiment Videos

Last Updated: Jul 7, 2026

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures

Published on: March 28, 2017

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene

Published on: April 1, 2019

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform

Published on: May 10, 2024

Area of Science:

Pharmacogenomics
Drug Metabolism

Background:

Warfarin dosing is complex and influenced by genetic factors.
Cytochrome P450 family 2 subfamily C member 9 (CYP2C9) is crucial for warfarin metabolism.
CYP2C9*2 and CYP2C9*3 alleles are known to affect warfarin dose requirements.

Purpose of the Study:

To investigate if CYP2C9 alleles beyond *2 and *3 influence low-warfarin dose requirements.
To determine the relevance of upstream CYP2C9 polymorphisms on warfarin dose and metabolism.

Main Methods:

Screening of CYP2C9 exons, intron-exon boundaries, and upstream sequences for novel polymorphisms.
Utilizing PCR-based genotyping for known and novel upstream polymorphisms in a larger patient cohort.
Analyzing the association between CYP2C9 genotypes and warfarin dose or S-warfarin total clearance.

Main Results:

Eight different upstream polymorphism sites were identified, with most in linkage disequilibrium with coding region polymorphisms.
Two specific upstream polymorphisms (T-1188C and DeltaG-2664DeltaT-2665) were found in both wild-type and variant individuals.
Neither individual upstream genotypes nor haplotype combinations predicted warfarin dose or S-warfarin clearance in individuals without coding region polymorphisms.

Conclusions:

Non-synonymous coding region polymorphisms in CYP2C9*2 and CYP2C9*3 are the main determinants of warfarin dose in UK Caucasians.
Upstream CYP2C9 polymorphisms are not significant independent predictors of warfarin dose requirements.