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The effect of CYP2D6 polymorphisms on the response to pain treatment for pediatric sickle cell pain crisis. J Pediatr 2007 Jun;150(6):623-6 PMID: 17517247 PMCID: PMC1978168

Pubmed ID

17517247

Abstract

OBJECTIVES: To test the hypothesis that children taking hydroxyurea who fail codeine therapy have an increase in reduced-functioning cytochrome P450 2D6 (CYP2D6) alleles.

STUDY DESIGN: Children with sickle cell disease presenting to an emergency department with a pain crisis unresponsive to codeine were genotyped. The proportion of children with reduced-functioning alleles and CYP2D6 enzyme activity scores < or = 1.5, were compared, by chi2 analysis, in children taking hydroxyurea and those with mild disease.

RESULTS: Of the 73 children completing the study, 42 had reduced-functioning alleles; 82% of the 27 children taking hydroxyurea had reduced-functioning alleles, versus 47% of 36 those with mild disease (P < .05). Activity scores were decreased in 78% of the children taking hydroxyurea and in 44% of those with mild disease (P < .05). The odds ratios of children taking hydroxyurea were 4.9 (95% confidence interval [CI] = 1.5 to 15.9) for having reduced-functioning alleles, and 4.4 (95% CI = 1.4 to 13.4) for having a low activity score.

CONCLUSIONS: Failing codeine therapy for a pain crisis while taking hydroxyurea is associated with an increase in reduced-functioning CYP2D6 alleles. We recommend genetic analysis or trial of a non-CYP2D6 analgesic for these children.

Author List

Brousseau DC, McCarver DG, Drendel AL, Divakaran K, Panepinto JA

Authors

David Brousseau MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
Amy L. Drendel DO Professor in the Pediatrics department at Medical College of Wisconsin
Julie A. Panepinto MD, MSPH Professor in the Pediatrics department at Medical College of Wisconsin




Scopus

2-s2.0-34248530257   42 Citations

MESH terms used to index this publication - Major topics in bold

Adolescent
Analgesics, Opioid
Anemia, Sickle Cell
Antisickling Agents
Child
Child, Preschool
Codeine
Cytochrome P-450 CYP2D6
Gene Deletion
Genotype
Humans
Hydroxyurea
Pain
Phenotype
Polymorphism, Single Nucleotide
jenkins-FCD Prod-310 bff9d975ec7f2d302586822146c2801dd4449aad