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Pharmacogenomics
Article
Data sources: UnpayWall
Pharmacogenomics
Article . 2013 . Peer-reviewed
Data sources: Crossref
Pharmacogenomics
Article . 2014
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OCT1 Genetic Variants Influence the Pharmacokinetics of Morphine in Children

Authors: Tsuyoshi, Fukuda; Vidya, Chidambaran; Tomoyuki, Mizuno; Raja, Venkatasubramanian; Pornswan, Ngamprasertwong; Vanessa, Olbrecht; Hope R, Esslinger; +2 Authors

OCT1 Genetic Variants Influence the Pharmacokinetics of Morphine in Children

Abstract

Large interindividual variability in morphine disposition could contribute to unpredictable variability in morphine analgesia and adverse events. Caucasian children have more adverse effects and slower morphine clearance than African-American children. To study variations in intravenous morphine pharmacokinetics in children, we examined the influence of genetic polymorphisms in OCT1.In 146 children undergoing adenotonsillectomy, 146 concentration-time profiles (2-4 measurements per patient) were available. Population pharmacokinetic analysis characterized the profiles in NONMEM(®) and tested OCT1 variants as covariates.Allometrically scaled post hoc Bayesian morphine clearance in homozygotes of loss-of-function OCT1 variants (n = 9, OCT1*2-*5/*2-*5) was significantly lower (20%) than in wild-type (n = 85, OCT1*1/*1) and heterozygotes (n = 52, OCT1*1/*2-*5; p < 0.05).Besides bodyweight, OCT1 genotypes play a significant role in intravenous morphine pharmacokinetics. Relatively high allelic frequencies of defective OCT1 variants among Caucasians may explain their lower morphine clearance and possibly higher frequencies of adverse events compared with African-American children. Original submitted 21 December 2012; Revision submitted 7 May 2013.

Keywords

Male, Postoperative Pain, Polymorphism, Genetic, Genotype, Morphine, Organic Cation Transporter 1, White People, Black or African American, Humans, Female, Child, Genetic Association Studies

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
92
Top 10%
Top 10%
Top 10%
bronze