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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...

Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants

Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants

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Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...

Therapeutic Drug Monitoring: Affecting Factors

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Therapeutic Drug Monitoring (TDM) is the clinical practice of measuring specific drug levels in a patient's blood or body tissues to manage and optimize therapy. TDM is crucial for drugs with narrow therapeutic windows, like warfarin and phenytoin, where incorrect doses can lead to treatment failure or severe side effects. This monitoring ensures the dosage administered is within a safe and effective range. The factors affecting therapeutic drug monitoring include:Patient-Specific Factors:a.

Dosage Regimen: Multiple Oral Dosage

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Understanding how a drug's concentration fluctuates within the body over time is crucial in pharmacokinetics, particularly with multiple oral doses. A graphical representation of multiple oral dosages provides insight into these dynamics. Typical accumulation curves of a drug's concentration in the body reveal a sawtooth pattern, indicating periodic peaks and troughs correlating with each dose administration and the drug's subsequent elimination.The plasma concentration at any time during an...

Drug toxicity: Idiosyncratic Reactions

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Related Experiment Video

Updated: May 16, 2026

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

Influence of ORM1 polymorphisms on the maintenance stable warfarin dosage.

Lian Sheng Wang¹, Jing Jing Shang, Shu Ya Shi

¹Pharmacogenetics Research Institute, Institute of Clinical Pharmacology of Central South University, Changsha, China. wang_liansheng@hotmail.com

European Journal of Clinical Pharmacology

|December 5, 2012

Summary

The ORM1 gene rs17650 polymorphism influences warfarin dosing. Patients with the ORM1 S variant require lower warfarin maintenance doses for effective anticoagulation.

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Last Updated: May 16, 2026

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
Clinical Pharmacology
Genetics

Background:

The ORM1 gene encodes a plasma drug binding protein.
ORM1 rs17650 polymorphism (S>F) affects drug binding, impacting antiretroviral therapy.
The influence of ORM1 rs17650 on warfarin therapy remains unexplored.

Purpose of the Study:

To investigate the association between ORM1 rs17650 polymorphism and warfarin dose requirements.
To determine if ORM1 genetic variation impacts warfarin therapy outcomes.

Main Methods:

A cohort of 191 Chinese patients on stable warfarin therapy was studied.
Genotyping included ORM1 rs17650, CYP2C9 rs1057910, and VKORC1 rs7294 polymorphisms.
Warfarin maintenance doses were analyzed in relation to genetic variations.

Main Results:

Warfarin dose showed partial correlation with VKORC1 rs7294, CYP2C9 rs1057910, and ORM1 rs17650.
Patients with wild-type alleles for all three genes required significantly higher mean warfarin doses.
ORM1 rs17650 S carriers (S/S or S/F genotypes) required lower maintenance doses.

Conclusions:

ORM1 is identified as a novel polymorphic gene influencing warfarin dose requirements.
ORM1 S allele carriers necessitate reduced maintenance warfarin doses for optimal anticoagulation.
This finding contributes to personalized warfarin therapy based on pharmacogenetics.