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Individualization in dosing regimens is the customization of medication doses for individual patients. Its necessity arises from the goal of maximizing therapeutic benefits while minimizing risks. This approach is pivotal because human responses to drugs can vary widely; what is effective for one person may be inadequate or excessive for another. Interpatient (intersubject) variability refers to differences in drug responses between individuals, while intrapatient (intrasubject) variability...
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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.

Kenneth E Thummel1, Yvonne S Lin

  • 1Department of Pharmaceutics, University of Washington, Seattle, WA, USA.

Methods in Molecular Biology (Clifton, N.J.)
|February 14, 2014
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Summary
This summary is machine-generated.

Drug metabolism variability, influenced by genetics and environment, causes unpredictable drug responses. Understanding these factors is key to personalized medicine and improved treatment outcomes.

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Area of Science:

  • Pharmacology and Pharmacogenomics
  • Drug Metabolism and Disposition

Background:

  • Drug efficacy, safety, and tolerability are highly variable between individuals due to factors influencing drug disposition.
  • Interindividual differences in drug metabolism lead to significant variations in systemic exposure (AUC, C max, C min) from fixed doses.
  • This variability poses challenges for achieving therapeutic goals and necessitates a move towards personalized medicine.

Purpose of the Study:

  • To explore the mechanistic basis of interindividual variability in drug disposition and response.
  • To highlight the role of drug metabolism in determining variable systemic exposure to medications.
  • To underscore the importance of understanding these variations for advancing personalized medicine.

Main Methods:

  • Review of established knowledge on factors affecting drug metabolism and disposition.
  • Analysis of intrinsic factors (genetics, age, sex, disease) and extrinsic factors (diet, environment, sunlight).
  • Examination of the role of cytochrome P450 enzymes and gene expression regulation in metabolic function.

Main Results:

  • Genetic variations in drug-metabolizing enzymes, particularly cytochrome P450s, can lead to complete absence or enhanced enzyme activity.
  • Gene expression can be up- or down-regulated by cellular environment, altering metabolic function (phenotype) in a time-dependent manner.
  • Both genetic and environmental factors contribute significantly to the wide range of drug responses observed in patients.

Conclusions:

  • Understanding the mechanistic basis of drug disposition variability is crucial for optimizing therapeutic treatments.
  • Personalized medicine approaches, informed by individual metabolic profiles, promise improved health outcomes.
  • Moving beyond empirical dosing requires a comprehensive understanding of drug metabolism and its influencing factors.