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CYP2D6 phenotype-specific codeine population pharmacokinetics
Journal of Pain & Palliative Care Pharmacotherapy
|January 7, 2015
Summary
This study developed a pharmacokinetic model for codeine metabolism, revealing how genetic variations impact morphine conversion. The model aids understanding of codeine
Area of Science:
- Pharmacology
- Pharmacokinetics
- Genetics
Background:
- Codeine metabolism and its metabolites' quantitative data are limited for prescribers.
- Genetic polymorphisms significantly influence drug metabolism pathways.
Purpose of the Study:
- To develop a pharmacokinetic pathway model for codeine and its metabolites.
- To incorporate the effects of genetic polymorphisms into the model.
- To quantitatively understand codeine's metabolic fate.
Main Methods:
- Studied phenotype-specific plasma concentrations of codeine and its metabolites.
- Developed a codeine pharmacokinetic pathway model.
- Built a population pharmacokinetic model for codeine.
Main Results:
- The model accurately fitted plasma time courses of codeine and metabolites.
- Morphine conversion from codeine varied by phenotype: 10% (poor), 40% (extensive), 51% (ultrarapid).
- Morphine-6-glucuronide formation from morphine varied: 4% (poor), 39% (extensive), 58% (ultrarapid).
Conclusions:
- A population pharmacokinetic model enhances understanding of codeine pathways.
- The model can simulate pharmacogenetic-based drug disposition.
- Integrating pharmacogenetics, population, and clinical pharmacokinetics advances personalized dosing.
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