Document Detail


Pharmacogenetics of neonatal opioid toxicity following maternal use of codeine during breastfeeding: a case-control study.
MedLine Citation:
PMID:  18719619     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
P Madadi; C J D Ross; M R Hayden; B C Carleton; A Gaedigk; J S Leeder; G Koren
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-08-20
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  85     ISSN:  1532-6535     ISO Abbreviation:  Clin. Pharmacol. Ther.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-12-18     Completed Date:  2009-01-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  31-5     Citation Subset:  AIM; IM    
Affiliation:
Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adult
Analgesics, Opioid / adverse effects*,  metabolism*,  therapeutic use
Apnea / chemically induced
Breast Feeding / adverse effects*
Case-Control Studies
Codeine / adverse effects*,  metabolism*,  therapeutic use
Cytochrome P-450 CYP2D6 / genetics*
Female
Genotype
Humans
Infant
Infant, Newborn
Milk, Human / chemistry*
Opioid-Related Disorders / etiology*,  genetics*,  physiopathology
Pain / drug therapy
Pharmacogenetics
Chemical
Reg. No./Substance:
0/Analgesics, Opioid; 76-57-3/Codeine; EC 1.14.14.1/Cytochrome P-450 CYP2D6
Comments/Corrections
Comment In:
Clin Pharmacol Ther. 2009 Jan;85(1):20-2   [PMID:  19092767 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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