• Oscar A Linares, David Daly, Annemarie Daly Linares, Darko Stefanovski, and Raymond C Boston.
• Plymouth Pharmacokinetic Modeling Study Group, Plymouth, Michigan, USA.
• Pain Med. 2014 May 1;15(5):791-806.

ObjectiveTo develop a framework for integrating pharmacogenetics with clinical pharmacokinetics for personalized oxycodone dosing based on a patient's CYP2D6 phenotype.DesignRandomized, crossover, double-blind, placebo-controlled. Subjects were genotyped as CYP2D6 ultra-rapid metabolizer, extensive metabolizer, or poor metabolizer phenotypes. Five subjects from each phenotype were randomly selected for inclusion in our study.SettingStudies were performed in silico.SubjectsThe subjects were male, age 26 years, height 181.2 cm, and weight 76.3 kg. They were healthy without comorbidities, and their medical examinations were normal.MethodsThe trajectories of phenotype-specific plasma oxycodone concentration-time profiles were analyzed using weighted nonlinear least-squares regression with WinSAAM software. A global two-stage population-based model data analysis procedure was used to analyze the studies. Clinical pharmacokinetics were calculated using the R package cpk, eliminating the need to perform hand-calculations.ResultsOur study shows how clinicians can reduce risk and increase effectiveness for oxycodone dosing by (1) determining the patient's likely metabolic response through testing a patient's CYP2D6 phenotype, and (2) calculating clinical pharmacokinetics specific to the patient's CYP2D6 phenotype to design a personalized oxycodone dosing regimen.ConclusionsPersonalized oxycodone dosing is a new tool for a clinician treating chronic pain patients requiring oxycodone. By expressing a patient's CYP2D6 phenotype pharmacokinetically, a clinician (at least theoretically) can improve the safety and efficacy of oxycodone and decrease the risk for iatrogenically induced overdose or death. Pharmacokinomics provides a general framework for the integration of pharmacogenetics with clinical pharmacokinetics into clinical practice for gene-based prescribing.Wiley Periodicals, Inc.

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