Therapy for Apnoea of Prematurity: A Retrospective Study on Effects of Standard Dose and Genetic Variability on Clinical Response to Caffeine Citrate in Chinese Preterm Infants

doi:10.1007/s12325-020-01544-2

	Therapy for Apnoea of Prematurity: A Retrospective Study on Effects of Standard Dose and Genetic Variability on Clinical Response to Caffeine Citrate in Chinese Preterm Infants
	He, Xin 1; Qiu, Jin-Chun 1; Lu, Ke-Yu 2; Guo, Hong-Li 1; Li, Ling 3; Jia, Wei-Wei 4; Ni, Ming-Ming 1; Liu, Yun 2; Xu, Jing 1; Chen, Feng 1
刊名	ADVANCES IN THERAPY
	2020-11-12
页码	20
关键词	Adenosine receptors AHR AOP Caffeine Phosphodiesterase Polymorphism Therapeutic drug monitoring
ISSN号	0741-238X
DOI	10.1007/s12325-020-01544-2
通讯作者	Chen, Feng(cy.chen508@gmail.com) ; Cheng, Rui(chengrui350@163.com)
英文摘要	Introduction Apnoea of prematurity (AOP) is among the most common diagnoses in the neonatal intensive care unit. Caffeine treatment is a preferred treatment choice. However, neonatal caffeine therapy results in significant intersubject variability. This study aimed to determine the effects of plasma caffeine levels based on standard dose and genetic variability on clinical response to caffeine citrate in Chinese preterm infants. Methods This single-center and retrospective study examined data from 112 preterm infants (< 35 weeks gestational age) between July 2017 and July 2018. Subjects were divided into apnoea-free (n = 48) and apnoeic (n = 64) groups, and their clinical outcomes were summarized. Liquid chromatography-tandem mass spectrometry was used to measure levels of caffeine and its primary metabolites. Eighty-eight single-nucleotide polymorphisms were chosen for genotyping by a MassARRAY system. Results Preterm infants in the apnoea-free group were associated with a reduction in the incidence of bronchopulmonary dysplasia and a reduced requirement for patent ductus arteriosus ligation. No significant association was observed between plasma-trough-concentration-to-dose (C-0/D) ratio and birth weight, gestational age, or postnatal age in either group. Polymorphisms in CYP1A2 and aryl hydrocarbon receptor (AHR) genes did not affect plasma caffeine levels. Polymorphisms in adenosine receptor genes ADORA1 (rs10920568 and rs12744240), ADORA2A (rs34923252 and rs5996696), and ADORA3 (rs10776727 and rs2298191), especially in AHR (rs4410790) and adenosine deaminase (rs521704), play critical roles in the interindividual response to caffeine therapy. Conclusions Genetic polymorphisms in caffeine's target receptors, but not the exposure levels based on the standard dosing, were associated with variable responses to caffeine therapy in preterm neonates. Future studies are needed to uncover how these genetic variants affect responses to caffeine therapy in this patient population.
资助项目	Scientific Research Foundation for Young Scholars at the Children's Hospital of Nanjing Medical University[ETYYQM2014024] ; Specially Appointed Medical Expert Project of Jiangsu Commission of Health (2019) ; Special fund for clinical research of Wu Jieping Medical Foundation[320.6750.2020-04-07] ; Nanjing Medical University Science and Technology Development Foundation[NMUB2019195]
WOS关键词	ARYL-HYDROCARBON RECEPTOR ; NECROTIZING ENTEROCOLITIS ; ADENOSINE RECEPTORS ; POLYMORPHISMS ; SLEEP ; ASSOCIATION ; EXPRESSION
WOS研究方向	Research & Experimental Medicine ; Pharmacology & Pharmacy
语种	英语
出版者	SPRINGER
WOS记录号	WOS:000588882800003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/292524]
专题	中国科学院上海药物研究所
通讯作者	Chen, Feng; Cheng, Rui
作者单位	1.Nanjing Med Univ, Dept Pharm, Childrens Hosp, Nanjing, Peoples R China 2.Nanjing Med Univ, Neonatal Intens Care Unit, Childrens Hosp, Nanjing, Peoples R China 3.China Pharmaceut Univ, Sch Basic Med & Clin Pharm, Nanjing, Peoples R China 4.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	He, Xin,Qiu, Jin-Chun,Lu, Ke-Yu,et al. Therapy for Apnoea of Prematurity: A Retrospective Study on Effects of Standard Dose and Genetic Variability on Clinical Response to Caffeine Citrate in Chinese Preterm Infants[J]. ADVANCES IN THERAPY,2020:20.
APA	He, Xin.,Qiu, Jin-Chun.,Lu, Ke-Yu.,Guo, Hong-Li.,Li, Ling.,...&Cheng, Rui.(2020).Therapy for Apnoea of Prematurity: A Retrospective Study on Effects of Standard Dose and Genetic Variability on Clinical Response to Caffeine Citrate in Chinese Preterm Infants.ADVANCES IN THERAPY,20.
MLA	He, Xin,et al."Therapy for Apnoea of Prematurity: A Retrospective Study on Effects of Standard Dose and Genetic Variability on Clinical Response to Caffeine Citrate in Chinese Preterm Infants".ADVANCES IN THERAPY (2020):20.