Morphine clearance in children: Does race or genetics matter?

Senthilkumar Sadhasivam, MD, MPH; Elke H. J. Krekels, MSc; Vidya Chidambaran, MD; Hope R. Esslinger, MPT; Pornswan Ngamprasertwong, MD; Kejian Zhang, MD, MBA; Tsuyoshi Fukuda, PhD; Alexander A. Vinks, PharmD, PhD

doi:10.5055/jom.2012.0119

Authors

Senthilkumar Sadhasivam, MD, MPH
Elke H. J. Krekels, MSc
Vidya Chidambaran, MD
Hope R. Esslinger, MPT
Pornswan Ngamprasertwong, MD
Kejian Zhang, MD, MBA
Tsuyoshi Fukuda, PhD
Alexander A. Vinks, PharmD, PhD

DOI:

https://doi.org/10.5055/jom.2012.0119

Keywords:

morphine, pharmacokinetics, children, genetics, UGT2B7

Abstract

Objective: Interindividual variability in analgesic response and adverse effects of opioids because of narrow therapeutic indices are major clinical problems. Morphine is an opioid commonly used in children to manage perioperative pain. Although size and age often are considered primary covariates for morphine pharmacokinetic models, the impact of other factors important in personalizing care such as race and genetic variations on morphine disposition is not well documented.

Design: Genotype blinded clinical observational pharmacokinetic study. One hundred forty-six African American and Caucasian children scheduled for elective outpatient adenotonsillectomy were enrolled in our prospective genotype blinded observational study with standard perioperative clinical care.

Setting: Tertiary care pediatric institution.

Interventions: Morphine bolus for intraoperative analgesia in children and pharmacokinetic analyses in different races.

Main outcome measures: Pharmacokinetics and pharmacogenetics of intravenous morphine in a homogeneous pediatric outpatient surgical pain population were evaluated.

Results: The authors observed that African American children have higher morphine clearance than Caucasian children. The increased clearance is directed toward the formation of morphine-3-glucuronide formation, rather than the formation of morphine-6-glucuronide. Common uridine diphosphate glucuronosyl transferase (UGT) 2B7 genetic variations (-161C>T and 802C>T) were not associated with observed racial differences in morphine’s clearance although the wild type of the UGT2B7 isozyme is more prevalent in the African Americans.

Conclusions: Race of the child is an important factor in perioperative intravenous morphine’s clearance and its potential role in personalizing analgesia with morphine needs further investigation.

Author Biographies

Senthilkumar Sadhasivam, MD, MPH

Department of Anesthesia, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio

Elke H. J. Krekels, MSc

Department of Anesthesia, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; Division of Clinical Pharmacology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio

Vidya Chidambaran, MD

Department of Anesthesia, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio

Hope R. Esslinger, MPT

Department of Anesthesia, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio

Pornswan Ngamprasertwong, MD

Department of Anesthesia, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio

Kejian Zhang, MD, MBA

Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio

Tsuyoshi Fukuda, PhD

Division of Clinical Pharmacology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio

Alexander A. Vinks, PharmD, PhD

Division of Clinical Pharmacology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio.

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