The Prevalence of Ultrarapid Metabolizers of Codeine in a Diverse Urban Population

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Abstract

Objective: To examine the prevalence of ultrarapid metabolizers of codeine among children in an ethnically diverse urban community. Study Design: Cross-sectional study. Setting: A tertiary care academic children’s hospital in the Bronx, New York. Subjects and Methods: In total, 256 children with nonsyndromic congenital sensorineural hearing loss were analyzed. DNA was assessed for 63 previously described single-nucleotide polymorphisms (SNPs) and copy number variants (CNVs) known to alter the function and expression of the CYP2D6 gene primarily responsible for codeine metabolism. The rate of CYP2D6 metabolism was predicted based on participants’ haplotype. Results: Ethnic distribution in the study subjects paralleled recent local census data, with the largest portion (115 children, 45.8%) identified as Hispanic or Latino. A total of 154 children (80.6%) had a haplotype that corresponds to extensive codeine metabolism, 18 children (9.42%) were identified as ultrarapid metabolizers (UMs), and 16 children (8.37%) were intermediate metabolizers. Only 3 children in our cohort (1.57%) were poor metabolizers. Patients identifying as Caucasian or Hispanic had an elevated incidence of UMs (11.3% and 11.2%, respectively) with extensive variability within subpopulations. Conclusions: The clinically significant rate of ultrarapid metabolizers reinforces safety concerns regarding the use of codeine and related opiates. A patient-targeted approach using pharmacogenomics may mitigate adverse effects by individualizing the selection and dosing of these analgesics.

Original languageEnglish (US)
JournalOtolaryngology - Head and Neck Surgery (United States)
DOIs
StatePublished - Jan 1 2018

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Codeine
Urban Population
Hispanic Americans
Cytochrome P-450 CYP2D6
Haplotypes
Opiate Alkaloids
Pharmacogenetics
Censuses
Tertiary Healthcare
Single Nucleotide Polymorphism
Analgesics
Cross-Sectional Studies
Safety
Gene Expression
DNA
Incidence

Keywords

  • cytochrome p450
  • metabolizer
  • pharmacogenomics
  • ultrarapid

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology

Cite this

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title = "The Prevalence of Ultrarapid Metabolizers of Codeine in a Diverse Urban Population",
abstract = "Objective: To examine the prevalence of ultrarapid metabolizers of codeine among children in an ethnically diverse urban community. Study Design: Cross-sectional study. Setting: A tertiary care academic children’s hospital in the Bronx, New York. Subjects and Methods: In total, 256 children with nonsyndromic congenital sensorineural hearing loss were analyzed. DNA was assessed for 63 previously described single-nucleotide polymorphisms (SNPs) and copy number variants (CNVs) known to alter the function and expression of the CYP2D6 gene primarily responsible for codeine metabolism. The rate of CYP2D6 metabolism was predicted based on participants’ haplotype. Results: Ethnic distribution in the study subjects paralleled recent local census data, with the largest portion (115 children, 45.8{\%}) identified as Hispanic or Latino. A total of 154 children (80.6{\%}) had a haplotype that corresponds to extensive codeine metabolism, 18 children (9.42{\%}) were identified as ultrarapid metabolizers (UMs), and 16 children (8.37{\%}) were intermediate metabolizers. Only 3 children in our cohort (1.57{\%}) were poor metabolizers. Patients identifying as Caucasian or Hispanic had an elevated incidence of UMs (11.3{\%} and 11.2{\%}, respectively) with extensive variability within subpopulations. Conclusions: The clinically significant rate of ultrarapid metabolizers reinforces safety concerns regarding the use of codeine and related opiates. A patient-targeted approach using pharmacogenomics may mitigate adverse effects by individualizing the selection and dosing of these analgesics.",
keywords = "cytochrome p450, metabolizer, pharmacogenomics, ultrarapid",
author = "Jordan Virbalas and Morrow, {Bernice E.} and Reynolds, {David M.} and Bent, {John P.} and Ow, {Thomas J.}",
year = "2018",
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language = "English (US)",
journal = "Otolaryngology - Head and Neck Surgery (United States)",
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T1 - The Prevalence of Ultrarapid Metabolizers of Codeine in a Diverse Urban Population

AU - Virbalas, Jordan

AU - Morrow, Bernice E.

AU - Reynolds, David M.

AU - Bent, John P.

AU - Ow, Thomas J.

PY - 2018/1/1

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N2 - Objective: To examine the prevalence of ultrarapid metabolizers of codeine among children in an ethnically diverse urban community. Study Design: Cross-sectional study. Setting: A tertiary care academic children’s hospital in the Bronx, New York. Subjects and Methods: In total, 256 children with nonsyndromic congenital sensorineural hearing loss were analyzed. DNA was assessed for 63 previously described single-nucleotide polymorphisms (SNPs) and copy number variants (CNVs) known to alter the function and expression of the CYP2D6 gene primarily responsible for codeine metabolism. The rate of CYP2D6 metabolism was predicted based on participants’ haplotype. Results: Ethnic distribution in the study subjects paralleled recent local census data, with the largest portion (115 children, 45.8%) identified as Hispanic or Latino. A total of 154 children (80.6%) had a haplotype that corresponds to extensive codeine metabolism, 18 children (9.42%) were identified as ultrarapid metabolizers (UMs), and 16 children (8.37%) were intermediate metabolizers. Only 3 children in our cohort (1.57%) were poor metabolizers. Patients identifying as Caucasian or Hispanic had an elevated incidence of UMs (11.3% and 11.2%, respectively) with extensive variability within subpopulations. Conclusions: The clinically significant rate of ultrarapid metabolizers reinforces safety concerns regarding the use of codeine and related opiates. A patient-targeted approach using pharmacogenomics may mitigate adverse effects by individualizing the selection and dosing of these analgesics.

AB - Objective: To examine the prevalence of ultrarapid metabolizers of codeine among children in an ethnically diverse urban community. Study Design: Cross-sectional study. Setting: A tertiary care academic children’s hospital in the Bronx, New York. Subjects and Methods: In total, 256 children with nonsyndromic congenital sensorineural hearing loss were analyzed. DNA was assessed for 63 previously described single-nucleotide polymorphisms (SNPs) and copy number variants (CNVs) known to alter the function and expression of the CYP2D6 gene primarily responsible for codeine metabolism. The rate of CYP2D6 metabolism was predicted based on participants’ haplotype. Results: Ethnic distribution in the study subjects paralleled recent local census data, with the largest portion (115 children, 45.8%) identified as Hispanic or Latino. A total of 154 children (80.6%) had a haplotype that corresponds to extensive codeine metabolism, 18 children (9.42%) were identified as ultrarapid metabolizers (UMs), and 16 children (8.37%) were intermediate metabolizers. Only 3 children in our cohort (1.57%) were poor metabolizers. Patients identifying as Caucasian or Hispanic had an elevated incidence of UMs (11.3% and 11.2%, respectively) with extensive variability within subpopulations. Conclusions: The clinically significant rate of ultrarapid metabolizers reinforces safety concerns regarding the use of codeine and related opiates. A patient-targeted approach using pharmacogenomics may mitigate adverse effects by individualizing the selection and dosing of these analgesics.

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