The effect of CYP2D6 polymorphisms on the response to pain treatment for pediatric sickle cell pain crisis.
OBJECTIVE
To test the hypothesis that children taking hydroxyurea who fail codeine therapy have an increase in reduced-functioning cytochrome P450 2D6 (CYP2D6) alleles.


METHODS
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.
Brousseau
David C
DC
Department of Pediatrics, Section of Emergency Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. dbrousse@mcw.edu
McCarver
D Gail
DG
Drendel
Amy L
AL
Divakaran
Karthika
K
Panepinto
Julie A
JA
D000293:Adolescent; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000755:Anemia, Sickle Cell / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D000986:Antisickling Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003061:Codeine / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
D000701:Analgesics, Opioid; D000986:Antisickling Agents; D019389:Cytochrome P-450 CYP2D6; D003061:Codeine; D006918:Hydroxyurea