title: ABCB1 genotype is associated with fentanyl requirements in critically ill children.
abstract: BackgroundThe gene ABCB1 encodes p-glycoprotein, a xenobiotic efflux pump capable of transporting certain opioids, including fentanyl. ABCB1 genotype has been previously associated with patient opioid requirements and may influence fentanyl dosing requirements in critically ill children.MethodsA diagnostically diverse cohort of 61 children who received a fentanyl infusion while admitted to the pediatric intensive care unit (PICU) were included in this study. We examined associations between fentanyl requirements, pain and sedation scores, serum fentanyl levels, and ABCB1 genotype.ResultsPatients with the AA allele at ABCB1 locus rs1045642 received less fentanyl compared with patients with the AG or GG allele. A multivariable model demonstrated that patients with the AA allele received 18.6 mcg/kg/day less fentanyl than patients with either the AG or GG allele (95% confidence interval -33.4 to -3.8 mcg/kg/day; P=0.014). Incorporating race in this model demonstrated a similar association, but did not reach the threshold for multiple testing.ConclusionABCB1 genotype rs1045642 AA is associated with fentanyl administration in this cohort of children admitted to the PICU, likely because of decreased expression and activity of p-glycoprotein. Prospective evaluation of the influence of ABCB1 in sedative-analgesia administration in critically ill children is warranted.
authors.affiliation: Department of Critical Care Medicine, Safar Center for Resuscitation Research and the Brain Care Institute at the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Horvat
authors.affiliation: Department of Critical Care Medicine, Safar Center for Resuscitation Research and the Brain Care Institute at the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Au
authors.affiliation: Department of Human Genetics, School of Nursing and the Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Yvette P
authors.initials: YP
authors.lastname: Conley
authors.affiliation: Department of Critical Care Medicine and Pediatrics, Safar Center for Resuscitation Research and the Brain Care Institute at the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.affiliation: Department of Pharmacy and Therapeutics, Center for Clinical Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Lingjue
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pharmacy and Therapeutics, Center for Clinical Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Poloyac
authors.affiliation: Department of Pharmacy and Therapeutics, Center for Clinical Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Empey
authors.affiliation: Department of Critical Care Medicine and Pediatrics, Safar Center for Resuscitation Research and the Brain Care Institute at the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Robert S B
authors.initials: RSB
authors.lastname: Clark
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000483:Alleles; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness; D004334:Drug Administration Schedule; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007223:Infant; D015278:Intensive Care Units, Pediatric; D008297:Male; D015999:Multivariate Analysis; D010146:Pain / Q000188:drug therapy*; D059408:Pain Management / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012189:Retrospective Studies
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000701:Analgesics, Opioid; D005283:Fentanyl