How to use drugs for pain management: from pharmacokinetics to pharmacogenomics

The promise of pharmacogenomics (PGx), i.e. the study of the role of inheritance in the individual variation in drug response lies in its potential to further identify the right drug and dosing regimen in every individual patient. Observations on the impact of cytochrome P450 (CYP) 2D6, the μ-opioid receptor μ 1 (OPRM1), UDP-glucuronosyl (UGT) 2B7 isoenzyme, efflux transporter P-glycoprotein (P-gp) and ATP-binding cassette B1 (ABCB1/multiple drug resistence 1 (MDR1) polymorphisms on opioid disposition are provided to illustrate the potential impact of PGx on pain management. PGx are, however, only one group of co-variates of interindividual variability. People differ and the interindividual phenotypic variability is the final result of maturation, genomic variation and environment. Other clinical characteristics, like ontogeny (i.e. age-dependent maturation), co-morbidity (e.g. hepatic or renal dysfunction) or co-medication should be considered together with the genomic variation. Population pharmacokinetic models hereby enable researchers to simultaneously assess the independent impact of different co-variates.

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