Effects of Gene Polymorphism on the Pharmacokinetics of Sufentanil in Children with Congenital Heart Disease
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2022.0115
- VernacularTitle:基因多态性对先天性心脏病儿童舒芬太尼药代动力学的影响
- Author:
Bi-lian LI
1
;
Si-yi WANG
2
;
Xue BAI
1
;
Yao LIU
2
;
Wei WEI
1
;
Yan-ping GUAN
2
;
Guo-ping ZHONG
2
;
Xing-rong SONG
1
Author Information
1. Department of Anesthesiology， Guangzhou Women and Children's Medical Center， Guangzhou Medical University， Guangzhou 510120， China
2. Institute of Clinical Pharmacology， School of Pharmaceutical Sciences， Sun Yat-sen University， Guangzhou 510080， China
- Publication Type:Journal Article
- Keywords:
gene polymorphism;
sufentanil （SUF）;
pediatric;
pharmacokinetics
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2022;43(1):124-132
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effects of gene polymorphism on the pharmacokinetics of sufentanil （SUF） in children with congenital heart disease undergoing interventional cardiac surgery. MethodsA total of 168 ASA grade Ⅱ patients aged 6~72 months and scheduled for interventional cardiac surgery were enrolled into the study. Anesthesia was induced by using propofol 2 mg·kg-1， SUF 0.3 μg·kg-1 and cisatracurium besilate 0.2 mg·kg-1. Propofol 8 mg·kg-1·h-1 was administered to maintain anesthesia. Blood samples were collected at 5， 10， 20， 30， 45， 60， 75， 90 min after administration of SUF by dilution sampling method. Plasma concentration of sufentanil was determined by UHPLC-MS/MS method and pharmacokinetic parameters were calculated by Phoenix WinnonlintmTM software. The genotypes were detected by matrix-assisted laser desorption ionization-time of flight mass spectrometry （MALDI-TOF MS）. The genotypes and pharmacokinetic data were analyzed by SNPStats software and the model with the smallest value of Akaike information criterion was chosen as the best model. ResultsThirty single nucleotide polymorphisms （SNPs） in 9 genes possibly involved in pharmacokinetics， pharmacodynamics related targets， metabolic enzymes， transporters and pathways of SUF were examined. ABCG2 rs2054576 and OPRM1 rs4870266 were found to be related to area under the curve （AUC） （P<0.05）. OPRM1 rs2236257 was correlated with the apparent volume of distribution （Vd） （P<0.05）. CYP3A4 rs2246709， OPRM1 rs2236257 and rs4870266 were associated with the drug clearance rate （CL） （P<0.05）. ConclusionGene polymorphisms of ABCG2 rs2054576，CYP3A4 rs2246709 and OPRM1 rs2236257， rs4870266 could significantly affect the pharmacokinetics of SUF in children undergoing interventional cardiac surgery.
