Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Jan 2009
Clinical TrialThe consequence of concomitantly present functional genetic variants for the identification of functional genotype-phenotype associations in pain.
Genetics-based personalized approaches to pain management have received a setback because of the nonreproducibility of functional genetic associations such as the pain-modulatory effect of the catechol-O-methyl transferase (COMT) gene 472G>A single-nucleotide polymorphism. Given that many of the pain-relevant genetic variants are common (allelic frequencies of 10-50%), we hypothesized that a major reason for difficulties in reproducing demonstrations of genetic influences on pain is the concomitant presence in a single individual of several functional genetic polymorphisms that act as confounders.
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Clin. Pharmacol. Ther. · Jan 2009
Review Practice GuidelineRational prescribing for patients with a reduced life expectancy.
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Clin. Pharmacol. Ther. · Jan 2009
CommentSafety issues of maternal drug therapy during breastfeeding.
Two goals when counseling breastfeeding mothers taking medication are protecting the infant from adverse events and permitting necessary maternal therapy. Madadi et al. report a case-control study of neonatal and maternal opioid toxicity after codeine administration. Therapeutic considerations in counseling breastfeeding mothers include susceptibility to drug toxicity of the very young and/or premature infant, significant interindividual variations in drug response, the dose-response relationship with respect to drug toxicity, and the role of pharmacogenetics in both the mother and the infant. These host factors may combine in a particular patient to act synergistically to produce an adverse reaction.
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Clin. Pharmacol. Ther. · Jan 2009
Pharmacogenetics of neonatal opioid toxicity following maternal use of codeine during breastfeeding: a case-control study.
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). ⋯ 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.