Related Experiment Video

Updated: Jun 15, 2026

Human Liver Spheroids from Peripheral Blood for Liver Disease Studies
09:51

Human Liver Spheroids from Peripheral Blood for Liver Disease Studies

Published on: January 27, 2023

Human liver expression of CYP2C8: gender, age, and genotype effects

Suresh Babu Naraharisetti1, Yvonne S Lin, Mark J Rieder

  • 1Departments of Medicinal Chemistry, University of Washington, Seattle, WA 98195-7610, USA.

Drug Metabolism and Disposition: the Biological Fate of Chemicals
|March 2, 2010
PubMed

Insights

This study found that variations in CYP2C8 genotype, age, or gender did not significantly affect CYP2C8 drug metabolism enzyme expression levels in human livers. Hepatic CYP2C8 and CYP3A4 protein levels were strongly correlated, suggesting common regulatory factors.

Area of Science:

  • Pharmacogenomics
  • Drug Metabolism
  • Enzyme Kinetics

Background:

  • CYP2C8 is a key drug-metabolizing enzyme, processing about 5% of prescribed drugs.
  • Genetic variations (polymorphisms) in CYP2C8 can alter drug clearance.
  • Limited data exists on CYP2C8 expression in human livers concerning genetic, age, and gender influences.

Purpose of the Study:

  • To investigate interindividual variability in CYP2C8 mRNA and protein expression in human livers.
  • To evaluate the impact of CYP2C8 genotype (*3, *4), age, and gender on hepatic CYP2C8 expression.
  • To assess correlations between CYP2C8 mRNA and protein levels with other CYP enzymes (CYP3A4, CYP2C members).

Main Methods:

  • Analysis of CYP2C8 mRNA and protein expression in 60 human livers from white individuals.
  • Genotyping for CYP2C8*3 and CYP2C8*4 polymorphisms.
  • Statistical evaluation of genotype, age, and gender effects on CYP2C8 expression and correlations with other CYP enzymes.

Main Results:

  • No significant effect of CYP2C8*3 or *4 genotype, age, or gender on CYP2C8 mRNA or protein levels was observed.
  • A trend towards decreased CYP2C8 protein in CYP2C8*1/*4 livers was noted (p=0.07).
  • Strong positive correlation between hepatic CYP2C8 and CYP3A4 protein levels (r=0.76, p<0.0001), suggesting shared regulation.

Conclusions:

  • Hepatic CYP2C8 expression is not significantly influenced by common genetic variations, age, or gender in the studied population.
  • The strong correlation between CYP2C8 and CYP3A4 suggests co-regulation mechanisms.
  • Further research is needed to understand the clinical implications of observed variations in CYP2C8 activity.

More Related Videos

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment08:59

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures10:44

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

Published on: March 28, 2017

Related Concept Videos

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes01:28

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,...
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...
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow

Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug binding...
Pharmacogenetics of Drug Metabolism: Overview01:27

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...
Hepatic Drug Excretion: Influencing Factors01:16

Hepatic Drug Excretion: Influencing Factors

The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...