阿立哌唑血清药物浓度/剂量比影响因素研究  

Study on the Influencing Factors in Serum Drug Concentration/Dose Ratio of Aripiprazole

作　　者：李琰 瞿发林 汪莉 刘曼华 陈颖 隋沂言 钱霖 Li Yan;Qu Falin;Wang Li;Liu Manhua;Chen Ying;Sui Yiyan;Qian Lin(Department of Pharmacy;Department of Psychiatry,No.904 Hospital of Joint Logistics Support Force,Jiangsu Changzhou 213003,China)

机构地区：[1]中国人民解放军联勤保障部队第九〇四医院药剂科,江苏常州213003 [2]中国人民解放军联勤保障部队第九〇四医院精神科,江苏常州213003

出　　处：《中国药师》2022年第3期455-457,共3页China Pharmacist

基　　金：江苏省药学会天晴临床药学基金(编号:Q2018110)。

摘　　要：目的:研究性别、年龄、联合用药、CYP2D6基因多态性等因素对服用阿立哌唑(ARI)患者浓度剂量比(C/D)的影响,为临床合理用药提供参考。方法:查阅本院2019~2020年服用ARI的住院患者病历,计算C/D值,考察年龄、性别、合并用药、CYP2D6基因多态性对患者ARI、ARI+脱氢阿立哌唑(DARI)C/D值的影响。结果:133例住院患者的ARI平均血药浓度为(240.74±171.00)ng·ml^(-1),平均C/D为(237.89±161.68)ng·ml^(-1)·mg^(-1)·kg^(-1);ARI+DARI浓度为(322.72±187.78)ng·ml^(-1),C/D为(304.95±194.73)ng·ml^(-1)·mg^(-1)·kg^(-1)。性别、年龄不影响C/D值及C^(+)/C^(+)(P>0.05)。联合丙戊酸组的ARI、ARI+DARI C/D值明显低于无合并用药组(P<0.05)。CYP2D6*2(AA)组ARI C/D值显著高于CYP2D6*2(GG)组(P<0.05)。CYP2D6*41(TT)组ARI C/D值显著高于CYP2D6*41(CC)组(P<0.01)。CYP2D6*2(TT)ARI+DARI C/D值显著高于CYP2D6*41(CC)组(P<0.01)。结论:ARI具有较大的个体间药动学差异,患者服用ARI后的C/D值与患者的CYP2D6*2、CYP2D6*10基因多态性以及合并丙戊酸有关,C^(+)/C^(+)可以间接反映ARI代谢速率,推荐进行常规的治疗药物监测,结合血药浓度及临床疗效调整、优化给药方案。Objective: To study the effects of sex, age, combined drug use and CYP2 D6 gene polymorphism on concentration/dose(C/D) in patients taking aripiprazole(ARI), so as to provide reference for clinical rational drug use. Methods: The medical records of inpatients taking ARI during 2019 and 2020 were consulted, the C/D was calculated, and the effects of age, sex, combined drug use and CYP2 D6 gene polymorphism on the C/D values of ARI and ARI+dehydroaripiprazole(DARI) were investigated. Results: The mean serum concentration of ARI was(240.74±171.00) ng ·ml^(-1), the mean C/D was(237.89±161.68)(ng·ml^(-1)·mg^(-1)·kg^(-1)), and that of ARI+DARI was(322.72±187.78) ng ·ml^(-1) and(304.95±194.73)(ng·ml^(-1)·mg^(-1)·kg^(-1)), respectively. Sex and age did not affect the C/D ratio and C^(+)/C^(+)(P>0.05). The C/D values of ARI and ARI+DARI in the group combined with valproic acid were significantly lower than those in the group treated without valproic acid(P<0.05). The C/D values of ARI in CYP2 D6*2(AA) group were significantly higher than those in CYP2 D6*2(GG) group(P<0.05). The C/D values of ARI in CYP2 D6*41(TT) group were significantly higher than those in CYP2 D6*41(CC) group(P<0.01). The C/D values of ARI+DARI in CYP2 D6*2(TT) group was significantly higher than those in CYP2 D6*41(CC) group(P<0.01).Conclusion: There are great individual pharmacokinetic differences in ARI. The C/D of patients after taking ARI is related to the polymorphism of CYP2 D6*2 and CYP2 D6*10 gene and the combination of valproic acid. C^(+)/C^(+) can indirectly reflect the metabolic rate of ARI. Routine therapeutic drug monitoring is recommended, and combined with the blood concentration and clinical efficacy, the administration regimen can be adjusted and optimized.

关 键 词：阿立哌唑 脱氢阿立哌唑 浓度剂量比 影响因素 CYP2D6 

分 类 号：R969.1[医药卫生—药理学]