M. Baber,1 S. Chaudhry,1 L. Kelly,1 C. Ross,2 B. Carleton,3 H. Berger,4 G. Koren1; 1The Hospital for Sick Children, Toronto, ON, Canada, 2University of British Columbia, Vancouver, BC, Canada, 3Child and Family Research Institute, Vancouver, BC, Canada, 4St. Michael's Hospital, Toronto, ON, Canada
BACKGROUND: Codeine is commonly prescribed following cesarean section for postpartum pain management despite evidence that some women do not achieve optimal analgesia. In an effort to improve postpartum pain therapy, this study’s objective was to explore interindividual differences in codeine intake and reported pain levels by examining the role of genetic polymorphisms in the codeine pharmacological pathway.
METHODS: This study consisted of a nested cohort of 98 women who took codeine for the first two days following cesarean section. Subjects reported their level of pain using the Visual Analog Scale (mm) one hour following each dose of codeine and were genotyped for select polymorphisms of the COMT, ABCB1, CYP2D6, UGT2B7 and OPRM1 genes. The primary endpoints of this study were mean pain score (mm) and mean and cumulative dose intake (mg/kg) for the first two days following cesarean section.
RESULTS: Univariate analysis revealed that maternal age was predictive of mean pain score (p=0.041). Significant differences in mean codeine consumption were seen among the genotypic groups of the OPRM1 A118G (p=0.001) and UGT2B7 C802T (p=0.015) variants. Mean codeine intake also differed between Asians and Caucasians (p=0.048). Multivariate analysis revealed that the OPRM1 A118G and UGT2B7 C802T variants are predictive of mean codeine intake by the study population overall (p=0.000) and by Caucasians (p=0.001).
CONCLUSION: Reported pain increases with maternal age. Asians require more codeine than Caucasians. OPRM1 A118G and UGT2B7 C802T variants predict codeine consumption in the cohort overall and among Caucasians. These findings will assist in individualizing codeine therapy during the postpartum period.