Opioid-induced respiratory depression: ABCB1 transporter pharmacogenetics
S Sadhasivam1, V Chidambaran1, X Zhang2
11] Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA [2] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
The Pharmacogenomics Journal
|October 15, 2014
Summary
Genetic variations in ABCB1 influence morphine
Area of Science:
- Pharmacogenomics
- Clinical Pharmacology
- Pediatric Anesthesiology
Background:
- Opioid-induced respiratory depression (RD) is a significant clinical concern, leading to mortality and brain injury.
- Morphine transport across the blood-brain barrier is mediated by the P-glycoprotein transporter (ABCB1/MDR1).
- ABCB1 genetic polymorphisms may alter morphine's central effects and toxicity.
Purpose of the Study:
- To investigate the association between common ABCB1 genetic variants and postoperative respiratory depression (RD) in children receiving intravenous morphine.
- To determine if specific ABCB1 genotypes correlate with RD leading to prolonged hospital stays after tonsillectomy.
Main Methods:
- A homogenous pediatric cohort of 263 children undergoing tonsillectomy was studied.
- Genotyping for common ABCB1 polymorphisms, specifically rs9282564, was performed.
- Clinical outcomes, including the incidence of RD and prolonged hospital stay, were assessed.
Main Results:
- Children with GG and GA genotypes of ABCB1 rs9282564 exhibited increased risk of RD-related prolonged hospital stays.
- Each copy of the minor allele (G) for rs9282564 amplified the odds of prolonged hospital stay due to postoperative RD by 4.7-fold (95% CI: 2.1-10.8, P=0.0002).
Conclusions:
- ABCB1 genetic variants, particularly rs9282564, are associated with significant risks of respiratory depression and prolonged hospitalization in pediatric patients receiving morphine.
- These findings highlight the importance of pharmacogenomic screening for ABCB1 polymorphisms to personalize opioid therapy and mitigate adverse events in children.
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