阿立哌唑治疗精神分裂症的血药浓度与临床效应关系研究

中国临床药理学与治疗学 ›› 2011, Vol. 16 ›› Issue (1): 76-81.

阿立哌唑治疗精神分裂症的血药浓度与临床效应关系研究

李建华, 钟华, 沈卫民, 孙菊水, 陈海支, 范振国, 卢桂华

浙江省湖州市第三人民医院精神科,湖州 313000,浙江

收稿日期:2010-10-09 修回日期:2010-12-25 发布日期:2020-09-16
通讯作者: 钟华,男,硕士,主任医师,研究方向:精神分裂症的基础与临床。Tel: 13757289077 E-mail: adsy@21cn.com
作者简介:李建华,男,学士,副主任医师,研究方向:精神分裂症的基础与临床。Tel: 13185289271 E-mail: lichienhua@sina.com
基金资助:
湖州市科技计划项目(2007YS44)

Relationship between serum concentration and clinical efficacy of aripiprazole in the treatment of patients with schizophrenia

LI Jian-hua, ZHONG Hua, SHEN Wei-min, SUN Ju-shui, CHEN Hai-zhi, FAN Zhen-guo, LU Gui-hua

Department of Psychiatry,the Third People's Hospital of Huzhou,Huzhou 313000,Zhejiang,China

Received:2010-10-09 Revised:2010-12-25 Published:2020-09-16

摘要/Abstract

摘要： 目的: 研究阿立哌唑治疗精神分裂症的血药浓度与临床效应之间关系,探索阿立哌唑血药浓度的治疗窗。方法: 采用前瞻性研究方法,应用非固定剂量药物治疗8周。以高效液相色谱仪测定阿立哌唑的谷浓度,阳性和阴性症状量表(PANSS)、临床总体印象-病情严重程度量表(CGI-SI)评定疗效,治疗时出现的症状量表(TESS)评定不良反应。采用受试者运筹特征曲线(ROC曲线)获得血药浓度的最佳截断值,结合四分位间距法推测阿立哌唑血药浓度的治疗窗。并分析血药浓度与药物剂量、临床疗效、不良反应等之间的相关性。结果: 入组80例患者,治疗有效47例、无效29例,另外4例脱落。总的不良反应发生率为 32.5%。阿立哌唑血药浓度与药物剂量、PANSS减分率及TESS分值间呈正相关,与CGI-SI分值呈负相关。药物剂量与疗效无相关性。最低有效血药浓度为 363 μg/L,发生不良反应的血药浓度阈值为 540 μg/L。有效组血药浓度的四分位间距为348~623 μg/L。血药浓度在350~540 μg/L 的范围内疗效较好,副反应较轻。结论: 阿立哌唑治疗精神分裂症的血药浓度与临床效应之间存在相关性,较适宜的治疗窗是350~540 μg/L。

关键词: 阿立哌唑, 精神分裂症, 血清药物浓度, 临床效应, 治疗窗

Abstract: AIM: To explore the relationship between serum concentration and clinical efficacy of aripiprazole in the treatment of patients with schizophrenia,and the suitable therapeutic window of aripiprazole.METHODS: Prospective study method was adopted.The dosages of aripiprazole were unfixed for eight weeks.The trough serum concentrations were determined by high performance liquid chromatography (HPLC).The clinical efficacy was evaluated with the Positive and Negative Syndrome Scale ( PANSS) and the Clinical Global Impression-Severity of Illnes (CGI-SI), side effects were done with the Treatment Emergent Symptom Scale(TESS).The optimized cutoff value of serum concentration was procured by the receiver operator curve (ROC), and the therapeutic window of aripiprazole was evaluated combining quartering interval.The correlation among serum concentration and dosage, therapeutic effect and side effect of aripiprazole were analyzed.RESULTS: 80 subjects were participated in the study, 47 cases were effective, 29 cases were ineffective, 4 cases were lost. The total side effect incidence rate was 32.5%.The trough serum concentration was significantly positive correlated with dosages, the decreasing ratios of PANSS scores and TESS scores,respectively, and the trough serum concentration was significantly negative correlated with CGI-SI scores.There was no significant correlation between dosages and therapeutic effect.The lowest effective trough serum concentration was 363 μg/L, the trough serum concentration threshold occurring side effects was 540 μg/L, the quartering interval of trough serum concentration in the effective group was 348-623 μg/L.The efficacy of aripiprazole was best and its side effects were mildest when serum aripiprazole levels were in the range of 350-540 μg/L.CONCLUSION: The serum concentration of aripiprazole in the treatment of patients with schizophrenia is correlated with clinical efficacy. The suitable therapeutic window for patients treated with aripiprazole is 350-540 μg/L.

Key words: Aripiprazole, Schizophrenia, Serum concentration, Clinical efficacy therapeutic window , , , ,

中图分类号:

R749.3

引用本文

李建华, 钟华, 沈卫民, 孙菊水, 陈海支, 范振国, 卢桂华. 阿立哌唑治疗精神分裂症的血药浓度与临床效应关系研究[J]. 中国临床药理学与治疗学, 2011, 16(1): 76-81.

LI Jian-hua, ZHONG Hua, SHEN Wei-min, SUN Ju-shui, CHEN Hai-zhi, FAN Zhen-guo, LU Gui-hua. Relationship between serum concentration and clinical efficacy of aripiprazole in the treatment of patients with schizophrenia[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(1): 76-81.

使用本文

0
/ / 推荐

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://manu41.magtech.com.cn/Jweb_clyl/CN/

https://manu41.magtech.com.cn/Jweb_clyl/CN/Y2011/V16/I1/76

参考文献

[1] 朱紫青,张明园. 第3代抗精神病药阿立哌唑研究进展[J]. 中国医院用药评价与分析,2005,5(2):121-123.
[2] Shapiro DA, Renock S, Arrington E, et al. Aripiprazole: A novel atypical antipsychotic drug with a unique and robust pharmacology[J]. Neuropsychopharmacology, 2003,28(8):1400-1411.
[3] McQuade R, Burris KD, Jordan S, et al. Aripiprazole: a dopamine-serotonin system stabilizer[J]. Int J Neuropsychopharmacol, 2002,5 (1):176.
[4] 何燕玲,张明园.阳性和阴性综合症量表及其应用[J]. 临床精神医学杂志, 1997, 7 (6) : 353.
[5] 张明园.精神科量表评定手册[M].上海:上海科学技术出版社,1993: 165-167.
[6] 温预关,施玉旋,王广发.反相高效液相色谱法测定人血浆中阿立哌唑的浓度[J].中国医院药学杂志,2006,26(1):50-52.
[7] 吕映华,郑青山.医学量表研究中的数学模型及其评价[J].中国临床药理学与治疗学 2007,12(6):690-696.
[8] 王传跃,向应强,翁永振,等.精神分裂症患者氯氮平维持治疗的治疗依从性、剂量及浓度研究[J].中华精神科杂志,2001,34(3):138-141.
[9] Bachmann CJ,Rieger-Gies A,Heinzel-Gutenbrunner M,et al. Large variability of aripiprazole and dehydroaripiprazole serum concentrations in adolescent patients with schizophrenia[J].Ther Drug Monit, 2008,30(4):462-466.
[10]Kirschbaum KM,Müller MJ,Malevani J,et al.Serum levels of aripiprazole and dehydroaripiprazole,clinical response and side effects[J].World J Biol Psychiatry,2008,9(3):212-218.
[11]左笑丛,刘世坤,朱运贵,等.阿立哌唑的血药浓度与其治疗精神分裂症疗效的相关性分析[J].中国新药与临床杂志,2006,25(8):601-605.
[12]Kirschbaum KM,Müller MJ,Zernig G,et al.Therapeutic monitoring of aripiprazole by HPLC with column-switching and spectrophotometric detection[J].Clin Chem, 2005,51(9):1718-1721.
[13]Molden E, Lunde H, Lunder N, et al.Pharmacokinetic variability of aripiprazole and the active metabolite dehydroaripiprazole in psychiatric patients[J].Ther Drug Monit,2006,28(6):744-749.
[14]Mallikaarjun S,Salazar DE,Bramer SL.Pharmacokinetics, tolerability, and safety of aripiprazole following multiple oral dosing in normal healthy volunteers[J].J Clin Pharmacol, 2004,44(2):179-187.
[15]国效峰,陈晋东,赵靖平,等.阿立哌唑治疗精神分裂症的随机双盲对照试验[J].医学临床研究,2006,23(5):716-718.

相关文章 15

[1] 李娜, 韩鸿璨, 王骏. 以药动学方法评价的抗精神分裂症药物人体生物等效性研究的一般考虑[J]. 中国临床药理学与治疗学, 2021, 26(12): 1419-1425.

[2] 杨世涛, 祝一虹, 唐文新. 阿立哌唑联合度洛西汀对难治性抑郁的疗效及对血管内皮生长因子的作用研究[J]. 中国临床药理学与治疗学, 2020, 25(8): 937-942.

[3] 闫盼, 施剑飞, 李静, 王晟东, 王姝琪, 汪程鹏, 宋明芬. DRD2和5-HTR2A基因多态性及其交互作用对奥氮平治疗精神分裂症疗效的影响[J]. 中国临床药理学与治疗学, 2020, 25(10): 1131-1138.

[4] 万萍，刘亮，张萍，张忠东. 奥氮平在精神分裂症中的血清药物浓度/剂量比影响因素研究[J]. 中国临床药理学与治疗学, 2019, 24(9): 1024-1029.

[5] 胡德凤，王轶虎，龙小宇，王广水. 甘麦大枣汤加减方联合认知行为干预对精神分裂症超高危人群的干预作用及对认知功能、生活质量及血清5-HT、MT、TSH水平的影响[J]. 中国临床药理学与治疗学, 2019, 24(5): 546-553.

[6] 陈连洲，李松华，蒲犇. 阿立哌唑联合草酸艾司西酞普兰对重度抑郁患者多巴胺、5-羟色胺和皮质醇的影响研究[J]. 中国临床药理学与治疗学, 2019, 24(4): 446-450.

[7] 樊垚，薛永，汪昕，陈雪菲，张旭，姚应水，沈冲. 载脂蛋白E基因多态性与利培酮所致体质量降低的关联研究[J]. 中国临床药理学与治疗学, 2019, 24(3): 288-295.

[8] 曹婷，李娜娜，蔡骅琳. 神经甾体在精神分裂症发病与治疗中作用的研究进展[J]. 中国临床药理学与治疗学, 2018, 23(6): 709-714.

[9] 崔力军，潘鑫，朱洁琳，李建华. 帕利哌酮与奥氮平治疗首发精神分裂症患者的疗效观察[J]. 中国临床药理学与治疗学, 2017, 22(4): 466-470.

[10] 周勇，陈雪芳，黄汉津. 氨磺必利治疗精神分裂症疗效以及安全性研究[J]. 中国临床药理学与治疗学, 2017, 22(10): 1152-1157.

[11] 陶怀, 魏钦令, 杨佳锦, 刘勇, 唐姝娟. 不同剂量帕潘立酮治疗对精神分裂症发育模型大鼠行为学的影响[J]. 中国临床药理学与治疗学, 2016, 21(9): 1001-1006.

[12] 杨艳，夏泳，朱长江，陈艳波. 阿立哌唑对氨磺必利所致高泌乳素血症的影响研究[J]. 中国临床药理学与治疗学, 2016, 21(6): 693-696.

[13] 杭荣华, 李业平, 吴明飞, 李瑞. 门诊精神分裂症患者药物治疗的依从性与不良反应、社会支持的关系[J]. 中国临床药理学与治疗学, 2014, 19(8): 912-915.

[14] 倪平, 吕海龙, 国效峰, 张丽丽, 许林勇. 利培酮与奥氮平对精神分裂症急性期的疗效及临床影响因素的比较[J]. 中国临床药理学与治疗学, 2014, 19(2): 182-185.

[15] 唐亚梅, 张向晖, 刘勇. 地佐环平诱导的精神分裂症发育模型大鼠脑组织去甲肾上腺素、5-羟色胺及代谢产物的浓度变化[J]. 中国临床药理学与治疗学, 2012, 17(7): 721-726.

编辑推荐

Metrics

阅读次数

全文

摘要

本文评价

摘要

参考文献

相关文章

编辑推荐

Metrics

本文评价

回顶部