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Influence of midazolam-related genetic polymorphism on conscious sedation during upper gastrointestinal endoscopy in a Korean population
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Influence of midazolam-related genetic polymorphism on conscious sedation during upper gastrointestinal endoscopy in a Korean population
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Journal Article
Influence of midazolam-related genetic polymorphism on conscious sedation during upper gastrointestinal endoscopy in a Korean population
2019
Overview
Genetic polymorphism can result in abnormal pharmacodynamics that subsequently leads to the individual variance in sedative effects and adverse reactions. The aim of this study was to elucidate the association between midazolam-related genetic polymorphism and sedative effects, including adverse reactions, under conscious sedation during upper gastrointestinal endoscopy. We prospectively enrolled 100 eligible patients undergoing upper gastrointestinal endoscopy. The efficacy of the sedation, adverse reactions, plasma concentration of midazolam and 1-hydroxymidazolam were investigated as well as the genetic polymorphism of
MDR1
and
CYP3A5
. The correlation between genetic polymorphism and sedative effects was assessed. Regarding
MDR1
gene, the plasma concentration of midazolam was greater in patients with CGC haplotype (
P
= 0.012), while it was lower in patients with CAC haplotype (
P
= 0.005) than in those with other haplotypes. However, genetic polymorphism of neither
MDR1
nor
CYP3A5
correlated with the plasma concentration of 1-hydroxymidazolam. CGT haplotype of
MDR1
was significantly correlated with sedation grade after midazolam administration (
P
= 0.042). In contrast, genetic polymorphism of
CYP3A5
was not correlated with sedation grade. There was no association between genetic polymorphism of
MDR1
or
CYP3A5
and selected adverse reactions related to midazolam. Genetic polymorphism of
MDR1
influences the concentration of midazolam and the sedation grade. However, it is not associated with adverse reactions such as paradoxical response and retrograde amnesia.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Adult
/ Aged
/ Amnesia
/ ATP Binding Cassette Transporter, Subfamily B - genetics
/ Cytochrome P-450 CYP3A - genetics
/ Female
/ Humanities and Social Sciences
/ Humans
/ Hypnotics and Sedatives - administration & dosage
/ Hypnotics and Sedatives - adverse effects
/ Hypnotics and Sedatives - blood
/ Male
/ Midazolam - administration & dosage
/ Midazolam - analogs & derivatives
/ Science
