Pharmacogenetics of Neonatal Opioid Toxicity Following Maternal Use of Codeine During Breastfeeding: A Case–Control Study
- 20 August 2008
- journal article
- Published by Wiley in Clinical Pharmacology & Therapeutics
- Vol. 85 (1), 31-35
- https://doi.org/10.1038/clpt.2008.157
Abstract
A large number of women receive codeine for obstetric pain while breastfeeding. Following a case of fatal opioid poisoning in a breastfed neonate whose codeine prescribed mother was a CYP2D6 ultrarapid metabolizer (UM), we examined characteristics of mothers and infants with or without signs of central nervous system (CNS) depression following codeine exposure while breastfeeding in a case–control study. Mothers of symptomatic infants (n = 17) consumed a mean 59% higher codeine dose than mothers of asymptomatic infants (n = 55) (1.62 (0.79) mg/kg/day vs. 1.02 (0.54) mg/kg/day; P = 0.004). There was 71% concordance between maternal and neonatal CNS depression. Two mothers whose infants exhibited severe neonatal toxicity were CYP2D6 UMs and of the UGT2B7*2/*2 genotype. There may be a dose–response relationship between maternal codeine use and neonatal toxicity, and strong concordance between maternal‐infant CNS depressive symptoms. Breastfed infants of mothers who are CYP2D6 UMs combined with the UGT2B7*2/*2 are at increased risk of potentially life‐threatening CNS depression. Clinical Pharmacology & Therapeutics (2008); 85, 1, 31–35 doi:10.1038/clpt.2008.157Keywords
This publication has 25 references indexed in Scilit:
- Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 duplicationThe Pharmacogenomics Journal, 2006
- ISOFORM SELECTIVITY AND KINETICS OF MORPHINE 3- AND 6-GLUCURONIDATION BY HUMAN UDP-GLUCURONOSYLTRANSFERASES: EVIDENCE FOR ATYPICAL GLUCURONIDATION KINETICS BY UGT2B7Drug Metabolism and Disposition, 2003
- The Transfer of Drugs and Other Chemicals Into Human MilkPediatrics, 2001
- Codeine and the Breastfed NeonateJournal of Human Lactation, 1993
- Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medicationAmerican Journal of Obstetrics and Gynecology, 1993
- Morphine metabolism in children.British Journal of Clinical Pharmacology, 1989
- Bioactivation of the narcotic drug codeine in human liver is mediated by the polymorphic monooxygenase catalyzing debrisoquine 4-hydroxylation (cytochrome P-450 dbl/bufI)Biochemical and Biophysical Research Communications, 1988
- Analgesie drugs in breast milk and plasma*Clinical Pharmacology & Therapeutics, 1981
- Respiratory sensitivity of the newborn infant to meperidine and morphineClinical Pharmacology & Therapeutics, 1965
- The Excretion of Drugs in Human Milk—A ReviewBJOG: An International Journal of Obstetrics and Gynaecology, 1947