基于治疗药物监测的丙戊酸钠缓释片血药浓度影响因素分析  

Influential factors of serum concentration for sodium valproate sustained-release tablets: Evidence from a routine therapeutic drug monitoring service

作　　者：陈宏镇 谢焕山 陈超端 于东港 卢浩扬[1] 王占璋[1] 倪晓佳[1] 尚德为[1,3] 温预关 CHEN Hong-zhen;XIE Huan-shan;CHEN Chao-duan;YU Dong-gang;LU Hao-yang;WANG Zhan-zhang;NI Xiao-jia;SHANG De-wei;WEN Yu-guan(Department of Pharmacy,The Affiliated Brain Hospital of Guangzhou Medical University,Guangzhou 510370,Guangdong Province,China;College of Pharmacy,Jinan University,Guangzhou 510632,Guangdong Province,China;Technology Guangdong Engineering Technology Research Center for Translational Mental Disorders,Guangzhou 210370,Guangdong Province,China)

机构地区：[1]广州医科大学附属脑科医院药学部,广东广州510370 [2]暨南大学药学院,广东广州510632 [3]广东省精神疾病转化医学工程技术研究中心,广东广州510370

出　　处：《中国临床药理学杂志》2020年第10期1216-1219,共4页The Chinese Journal of Clinical Pharmacology

基　　金：广东省省级科技计划基金资助项目(2019B030316001);广东省卫生计生适宜推广基金资助项目(粤卫办函[2018]326号);广州市科技计划基金资助项目(20180501009);广州市医学重点学科建设基金资助项目(2017-2019)。

摘　　要：目的基于临床治疗药物监测,探究性别、年龄、给药剂量、细胞色素P(CYP)2C19基因多态性对服用丙戊酸钠缓释片住院患者稳态血药浓度的影响,并为临床合理用药提供参考。方法回顾性收集2018年5月至2018年9月在广州医科大学附属脑科医院服用丙戊酸钠缓释片住院患者的性别、年龄、给药剂量、合并用药、血药浓度、CYP2C19基因型等基本信息。丙戊酸钠血药浓度用化学发光微粒子免疫分析法测定。用SPSS 16.0软件对以上数据进行统计分析。结果女性患者剂量校正后的丙戊酸钠血药浓度显著高于男性患者(P<0.01),分别为(88.87±33.14)和(78.74±23.56)μg·mL^-1·mg^-1·d;随着年龄的增大,剂量校正后的血药浓度越大,但组间差异无统计学意义(P>0.05);CYP2C19的基因多态性对丙戊酸血药浓度没有显著的影响(P>0.05);在多重线性回归分析中,仅有给药剂量及性别差异有统计学意义。结论丙戊酸钠缓释片的血药浓度影响因素复杂,具有较大的个体间药代动力学差异。性别以及给药剂量是影响丙戊酸血药浓度的重要因素,年龄差异对丙戊酸钠血药浓度的影响不具有临床意义,CYP2C19基因型不建议作为制定给药方案的依据。Objective Based on the data from a routine therapeutic drug monitoring service, the influence of sex, age, dosage and cytochrome P(CYP) 2C19 genetics on the serum concentration of sodium valproate in patients were investigated. Methods The clinical data of psychiatric inpatients treated with sodium valproate sustained-release tablets were reviewed form May 2018-Aug 2018. A Chemiluminescence Microparticle Immuno Assay was used to detect the serum concentration of sodium valproate. All the data were analyzed by SPSS 16.0. Results The dose adjusted valproate serum concentration of female patiants are significantly higher than that in male patients(P<0.01), which were(88.87±33.14) and(78.74±23.56) μg·mL^-1·mg^-1·d, respectively. As the age increases, the greater the dose adjusted valproate serum concentration, but there was no significant difference among different age groups. The CYP2C19 genotypes do not significantly influenced the serum concentration of sodium valproate(P>0.05). Multiple linear regression showed that only sex and dosage significantly influenced the serum concentration of sodium valproate. Conclusion The influential factors of serum concentration for sodium valproate are complicated and the pharmacokinetic showed a significant individual difference. The present study shows that gender and dosage significantly influence VPA serum concentration.In addition,we conclude that CYP2 C19 genotype is not relevant for variability in sodium valproate exposure.

关 键 词：丙戊酸钠缓释片 治疗药物监测 血清药物浓度 细胞色素P4502C19基因多态性 

分 类 号：R971[医药卫生—药品]