Is It Truly the Answer? Personalized Oxycodone Dosing Based on Pharmacogenetic Testing and the Corresponding Pharmacokinetics

Abstract

Dear Editor, It is with great interest that we read the article by Linares and colleagues, “Personalized oxycodone dosing: using pharmacogenetic testing and clinical pharmacokinetics to reduce toxicity risk and increase effectiveness”, published in the April 2014 issue of Pain Medicine [1]. In this study, a randomized, crossover, double-blind, placebo-controlled investigation was conducted, with a total of 15 healthy male subjects phenotyped as CYP2D6 ultra-rapid metabolizer (UM), extensive metabolizer (EM), or poor metabolizer (PM) to obtain mean plasma oxycodone concentrations at each time point in each phenotype, and subsequently to be used to generate the phenotype-specific drug clearance parameter, in an attempt to “develop a frame for integrating pharmacogenetics with clinical pharmacokinetics for personalized oxycodone dosing based on a patient’s CYP2D6 phenotype.” The authors utilized a plethora of complicated computational formulae in advanced pharmacokinetics, and applied them to the subjects whose CYP2D6 polymorphisms were known, via genetic testing, to determine the target therapeutic plasma oxycodone concentrations, and finally determined the personalized oxycodone dose with the utilization of “phenotype-specific clinical pharmacokinetics” after repeated pharmacokinetic computations. The authors concluded that “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”. We respect the painstaking effort of the Linares and colleagues devoted to this highly technical 16-page work …