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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...
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance01:23

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...
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...
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Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Drug toxicity: Idiosyncratic Reactions01:16

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...

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Updated: Jun 5, 2026

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures
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Published on: March 28, 2017

CYP2C19 variation and citalopram response.

David A Mrazek1, Joanna M Biernacka, Dennis J O'Kane

  • 1Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA. mrazek.david@mayo.edu

Pharmacogenetics and Genomics
|December 31, 2010
PubMed
Summary
This summary is machine-generated.

Genetic variations in CYP2C19 influence citalopram tolerance and remission in patients. Specifically, the inactive 2C19*2 allele reduced tolerance, while poor metabolism genotypes were linked to higher remission rates.

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Thermostabilization, Expression, Purification, and Crystallization of the Human Serotonin Transporter Bound to S-citalopram
12:21

Thermostabilization, Expression, Purification, and Crystallization of the Human Serotonin Transporter Bound to S-citalopram

Published on: November 27, 2016

Area of Science:

  • Pharmacogenomics
  • Clinical Pharmacology
  • Psychiatry

Background:

  • Cytochrome P450 (CYP) gene variations affect psychotropic drug metabolism.
  • Citalopram, an antidepressant, is primarily metabolized by CYP2C19 and CYP3A4, with CYP2D6 playing a secondary role.

Purpose of the Study:

  • To investigate the association between CYP2C19 and CYP2D6 gene variations and treatment outcomes with citalopram.
  • To examine the impact of these genetic variations on depressive symptom remission and citalopram tolerance.

Main Methods:

  • Analysis of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) sample.
  • Focus on White non-Hispanic patients (n=1074) adherent to the study protocol.
  • Examination of CYP2C19 and CYP2D6 genotypes in relation to citalopram tolerance and remission.

Main Results:

  • Patients with the inactive CYP2C19 2C19*2 allele showed significantly lower odds of citalopram tolerance (P=0.02).
  • CYP2C19 genotypes associated with decreased metabolism trended towards lower tolerance (P=0.06).
  • Patients with poor metabolism CYP2C19 genotypes were more likely to achieve remission if tolerant to citalopram (P=0.03). No significant association was found for CYP2D6 variations.

Conclusions:

  • CYP2C19 genetic variations are significantly associated with citalopram tolerance and remission in White non-Hispanic patients.
  • Findings suggest potential for genotype-guided antidepressant selection, despite study limitations like the absence of serum drug levels.