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Pharmacogenomics for the forensic toxicologist.

Thomas C Kupiec1, Vishnu Raj, Nicole Vu

  • 1Analytical Research Laboratories, 840 Research Parkway, Suite 546, Oklahoma City, OK 73104, USA.

Journal of Analytical Toxicology
|April 20, 2006
PubMed
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Pharmacogenomics studies how genes affect drug response, crucial for reducing adverse drug reactions. Understanding genetic variations in drug metabolism and transport can explain unexpected drug concentrations and guide personalized medicine.

Area of Science:

  • Pharmacogenomics
  • Genetics
  • Drug Metabolism

Background:

  • Adverse drug reactions (ADRs) are a significant healthcare burden, costing billions annually.
  • Interindividual differences in drug response are often due to genetic variations (polymorphisms).
  • Genetic polymorphisms affect drug-metabolizing enzymes (like CYP450), transporters, and drug targets.

Purpose of the Study:

  • To review the pharmacogenomics of common drug-metabolizing enzymes, transport proteins, and targets.
  • To highlight the role of pharmacogenomics in forensic toxicology using examples like tramadol, methadone, and oxycodone.
  • To emphasize considering genotype-mediated drug levels in cases of dose-concentration discrepancies.

Main Methods:

  • Literature review focusing on pharmacogenomics of drug disposition.

Related Experiment Videos

  • Analysis of genetic polymorphisms in drug-metabolizing enzymes, particularly CYP enzymes.
  • Case examples illustrating pharmacogenomic principles in forensic toxicology.

    • Main Results:

    • Genetic polymorphisms in drug-metabolizing enzymes, such as CYP2D6, are well-documented and impact drug metabolism.
    • There is a need for more research into the role of transport proteins and drug targets in pharmacogenomics.
    • Pharmacogenomics can explain incongruence between prescribed drug doses and observed plasma concentrations.

    Conclusions:

    • Pharmacogenomics is essential for understanding and mitigating adverse drug reactions.
    • Genetic variations significantly influence drug disposition, affecting efficacy and safety.
    • Considering patient genotype is vital for accurate drug dosing and forensic toxicology assessments.