Renee C B Manworren1, Lauren Jeffries, Ashley Pantaleao, Richard Seip, William T Zempsky, Gualberto Ruaño. 1. *Division of Pain and Palliative Medicine, Connecticut Children's Medical Center, Hartford, CT †Department of Pediatrics, University of Connecticut School of Medicine, Farmington §Genetics Research Center, Hartford Hospital, Hartford ‡Center for the Advancement in Managing Pain, University of Connecticut School of Nursing Storrs ∥Genetics Research Center, Hartford Hospital, Genomas Laboratory of Personalized Health Inc, Hartford, CT.
Abstract
OBJECTIVES: Genetic variants in pharmacokinetic genes can alter the effectiveness and increase the risks of using analgesics to treat pain. The purpose of this retrospective study is to describe the clinical experiences that led to pharmacogenetic testing of pediatric pain management program patients for alterations in the CYP2D6, CYP2C19, and CYP2C9 genes and correlate the analgesic efficacy and adverse analgesic effects with the gene-specific findings and Metabolic Reserve (MR) index. MATERIALS AND METHODS: Nineteen patients were referred for pharmacogenetic testing between February 2010 and December 2013 due to analgesic ineffectiveness or adverse analgesic effects. CYP2D6, CYP2C19, and CYP2C9 functional status was inferred from genotyping; and MR calculated. Data from the available inpatient and outpatient medical records from January 2007 to May 2014 for these patients were reviewed and extracted to characterize patient analgesic response phenotype. RESULTS: Significant CYP2D6 genetic variants were identified in 16 of the 19 (84%) patients: 4 were ultra-rapid metabolizers, 8 were deficient, 3 were poor metabolizers, and 1 was CYP2D6 null metabolizer. Of the 3 patients with functional CYP2D6 status, 2 were CYP2C19 null metabolizers. The MR scores ranged from 3.0 to 7.0, with a bimodal distribution with high frequencies corresponding to 4.0/4.5 and 7.0. DISCUSSION: Clinical evaluation of analgesic ineffectiveness and adverse effects led to the high likelihood of identifying patients with CYP2D6, CYP2C19, and CYP2C9 alleles associated with alterations in analgesic metabolism. Further research is needed to integrate pharmacogenetic and clinical information into anticipatory guidance for pharmacogenetic testing and analgesic prescribing to children with pain.
OBJECTIVES: Genetic variants in pharmacokinetic genes can alter the effectiveness and increase the risks of using analgesics to treat pain. The purpose of this retrospective study is to describe the clinical experiences that led to pharmacogenetic testing of pediatric pain management program patients for alterations in the CYP2D6, CYP2C19, and CYP2C9 genes and correlate the analgesic efficacy and adverse analgesic effects with the gene-specific findings and Metabolic Reserve (MR) index. MATERIALS AND METHODS: Nineteen patients were referred for pharmacogenetic testing between February 2010 and December 2013 due to analgesic ineffectiveness or adverse analgesic effects. CYP2D6, CYP2C19, and CYP2C9 functional status was inferred from genotyping; and MR calculated. Data from the available inpatient and outpatient medical records from January 2007 to May 2014 for these patients were reviewed and extracted to characterize patient analgesic response phenotype. RESULTS: Significant CYP2D6 genetic variants were identified in 16 of the 19 (84%) patients: 4 were ultra-rapid metabolizers, 8 were deficient, 3 were poor metabolizers, and 1 was CYP2D6 null metabolizer. Of the 3 patients with functional CYP2D6 status, 2 were CYP2C19 null metabolizers. The MR scores ranged from 3.0 to 7.0, with a bimodal distribution with high frequencies corresponding to 4.0/4.5 and 7.0. DISCUSSION: Clinical evaluation of analgesic ineffectiveness and adverse effects led to the high likelihood of identifying patients with CYP2D6, CYP2C19, and CYP2C9 alleles associated with alterations in analgesic metabolism. Further research is needed to integrate pharmacogenetic and clinical information into anticipatory guidance for pharmacogenetic testing and analgesic prescribing to children with pain.