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Using Cholesky Decomposition to Explore Individual Differences in Longitudinal Relations between Reading Skills
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Sources of Interindividual Variability.

Yvonne S Lin1, Kenneth E Thummel2, Brice D Thompson2

  • 1Department of Pharmaceutics, University of Washington, Seattle, WA, USA. yvonlin@uw.edu.

Methods in Molecular Biology (Clifton, N.J.)
|July 17, 2021
PubMed
Summary
This summary is machine-generated.

Individual differences in drug metabolism cause varied drug responses. Understanding these variations is key to personalized medicine and improved patient outcomes.

Keywords:
DiseaseGenderInterindividual variabilityPharmacogenomicsPregnancy

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Area of Science:

  • Pharmacology
  • Genetics
  • Personalized Medicine

Background:

  • Drug efficacy, safety, and tolerability depend on factors influencing drug disposition.
  • Variability in drug response arises from differences in drug metabolism, affecting systemic exposure (AUC, Cmax, Cmin).
  • Both intrinsic (genetics, age, sex, disease) and extrinsic (diet, environment, microbiome) factors contribute to interindividual differences in drug biotransformation.

Purpose of the Study:

  • To explore the mechanistic basis for variability in drug disposition and response.
  • To highlight the role of drug metabolism in achieving personalized medicine.
  • To move beyond empirical dosing towards tailored therapeutic strategies.

Main Methods:

  • Review of existing literature on drug metabolism and interindividual variability.
  • Analysis of intrinsic and extrinsic factors affecting drug biotransformation.
  • Discussion of genetic variations and gene expression changes impacting metabolic function.

Main Results:

  • Genetic variations can lead to absence or enhanced expression of drug-metabolizing enzymes.
  • Gene expression can be upregulated or downregulated, altering metabolic function.
  • Understanding these mechanisms is crucial for predicting drug response.

Conclusions:

  • Interindividual differences in drug metabolism significantly impact therapeutic outcomes.
  • Personalized medicine requires a deep understanding of the mechanistic basis of drug disposition variability.
  • Tailored dosing strategies based on individual metabolic profiles will improve health outcomes.