Related Experiment Video

Updated: May 9, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
07:23

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

Published on: July 29, 2014

OCT1 genetic variants influence the pharmacokinetics of morphine in children

Tsuyoshi Fukuda1, Vidya Chidambaran, Tomoyuki Mizuno

  • 1Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, OH, USA.

Pharmacogenomics
|July 18, 2013
PubMed

Insights

Genetic variations in the OCT1 gene significantly impact how children process morphine, affecting its effectiveness and side effects. This finding helps explain differences in morphine response between racial groups.

Area of Science:

  • Pharmacogenomics
  • Clinical Pharmacology
  • Pediatric Anesthesiology

Background:

  • Interindividual variability in morphine pharmacokinetics can lead to unpredictable analgesia and adverse events.
  • Caucasian children exhibit more adverse effects and slower morphine clearance compared to African-American children.

Purpose of the Study:

  • To investigate the influence of genetic polymorphisms in the OCT1 gene on intravenous morphine pharmacokinetics in children.
  • To understand the role of OCT1 variants in morphine disposition and its clinical implications.

Main Methods:

  • Population pharmacokinetic analysis of 146 concentration-time profiles from children undergoing adenotonsillectomy.
  • Utilized NONMEM(®) software to characterize pharmacokinetic profiles.
  • Tested OCT1 variants as covariates in the pharmacokinetic model.

Main Results:

  • Morphine clearance was significantly lower (20%) in homozygotes of loss-of-function OCT1 variants compared to wild-type and heterozygotes (p < 0.05).
  • Allometrically scaled post hoc Bayesian clearance revealed significant differences based on OCT1 genotype.

Conclusions:

  • OCT1 genotypes, in addition to body weight, significantly influence intravenous morphine pharmacokinetics in children.
  • High frequencies of defective OCT1 variants in Caucasians may explain their reduced morphine clearance and increased adverse event rates compared to African-Americans.
Abstract

Related Concept Videos

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...
Principles of Pharmacogenetics: Types of Genetic Variants01:27

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...
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,...
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...
Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses a challenge in...
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...