CYP2D6 pharmacogenetic and oxycodone pharmacokinetic association study in pediatric surgical patients

• Published in: Pharmacogenomics Vol. 18; no. 4; pp. 337 - 348
• Main Authors: Balyan, Rajiv, Mecoli, Marc, Venkatasubramanian, Raja, Chidambaran, Vidya, Kamos, Nichole, Clay, Smokey, Moore, David L, Mavi, Jagroop, Glover, Chris D, Szmuk, Peter, Vinks, Alexander, Sadhasivam, Senthilkumar
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.03.2017
• Subjects: Administration, Oral; Adolescent; Analgesics; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - pharmacokinetics; Child; Child, Preschool; Children; CYP2D6; CYP2D6 protein; Cytochrome P-450 CYP2D6 - genetics; Cytochrome P450; Drug dosages; Female; Genetic variability; Genotype & phenotype; Genotypes; Humans; Male; Metabolism; Metabolites; Narcotics; Oxycodone; Oxycodone - administration & dosage; Oxycodone - pharmacokinetics; Pain management; Pain, Postoperative - blood; Pain, Postoperative - genetics; Pain, Postoperative - prevention & control; Patients; Pediatrics; pharmacogenetics; Pharmacogenetics - methods; Pharmacokinetics; Phenotypes; Pilot Projects; Plasma levels; Prospective Studies; Ratios; surgical pain; oxycodone; pharmacokinetics; CYP2D6; pharmacogenetics; pediatrics; surgical pain
• ISSN: 1462-2416; 1744-8042; 1744-8042
• DOI: 10.2217/pgs-2016-0183

Oxycodone is partly metabolized to the active metabolite oxymorphone by hepatic CYP2D6 in the liver. Significant genetic variability in CYP2D6 activity affects oxymorphone formation. This study aimed to associate genotype and oxycodone's metabolism. 30 children were administered oral oxycodone postoperatively. Plasma levels of oxycodone and oxymorphone, and genotype were analyzed. genotype and oxycodone metabolism phenotype were determined based on CYP2D6 total activity score (TAS) and metabolism phenotype: poor metabolizer (PM), intermediate metabolizer (IM), extensive metabolizer (EM) or ultrarapid metabolizer (UM). Compared with PM/IM subjects, significantly greater oxymorphone exposure was seen in EM subjects (p = 0.02 for C , p = 0.016 for AUC and p = 0.026 for AUC ). Similarly, higher TAS value was found to be associated with greater oxymorphone exposure. Higher conversion of oxycodone to oxymorphone was observed in EM subjects compared with PM/IM subjects (p = 0.0007 for C , p = 0.001 for AUC and p = 0.004 for AUC ). phenotypes explain metabolism of oxycodone in children, and oxymorphone exposure is higher in EM phenotype. Further studies are needed to predict the occurrence of adverse event and tailor oxycodone dose for a specific phenotype.