1、硕 士 学 位 论 文论文20062009 年血药浓度监测回顾性分析Retrospectively analysis of blood concentration monitoring of Qilu hospital of Shandong university between 2006 and 2009Shandong University Master,s Thesis山东大学硕士学位论文2原 创 性 声 明本人郑重声明：所呈交的学位论文，是本人在导师的指导下，独立进行研究所取得的成果。除文中已经注明引用的内容外，本论文不包含任何其他个人或集体已经发表或撰写过的科研成果。对本文的研究作出
2、重要贡献的个人和集体，均已在文中以明确方式标明。本声明的法律责任由本人承担。论文作者签名： 日 期： 关于学位论文使用授权的声明本人同意学校保留或向国家有关部门或机构送交论文的印刷件和电子版，允许论文被查阅和借阅；本人授权山东大学可以将本学位论文的全部或部分内容编入有关数据库进行检索，可以采用影印、缩印或其他复制手段保存论文和汇编本学位论文。(保密论文在解密后应遵守此规定)论文作者签名： 导师签名： 日 期： 目 录山东大学硕士学位论文3中文摘要1英文摘要3符号说明6前言7第一部分 四种抗癫痫药物血药浓度监测结果回顾分析1 仪器与试剂92 方法92.1 采集血样92.2 测定方法92.3 血药
3、浓度判断标准93 结果93.1 2006-2009 年 4 种抗癫痫药物各年度血药浓度监测结果103.1.1 2006 年 4 种抗癫痫药物血药浓度监测结果103.1.2 2007 年 4 种抗癫痫药物血药浓度监测结果123.1.3 2008 年 4 种抗癫痫药物血药浓度监测结果143.1.4 2009 年 4 种抗癫痫药物血药浓度监测结果163.2 2006-2009 年 4 种抗癫痫药物各年度汇总分析183.2.1 2006 年 4 种抗癫痫药物监测汇总分析183.2.2 2007 年 4 种抗癫痫药物监测汇总分析193.2.3 2008 年 4 种抗癫痫药物监测汇总分析203.2.4 2
4、009 年 4 种抗癫痫药物监测汇总分析213.3 2006-2009 年 4 种抗癫痫药物监测分析 223.3.1 2006-2009 年丙戊酸钠血药浓度测定结果分析 223.3.2 2006-2009 年卡马西平血药浓度测定结果分析 233.3.3 2006-2009 年苯巴比妥血药浓度测定结果分析 243.3.4 2006-2009 年苯妥英钠血药浓度测定结果分析 253.4 2006-2009 年 4 种抗癫痫药物监测人次、年龄和性别汇总分析263.4.1 2006-2009 年 4 种抗癫痫药物监测人次所占比例 26山东大学硕士学位论文43.4.2 2006-2009 年 4 种抗癫
5、痫药物应用患者年龄汇总分析 273.4.3 2006-2009 年 4 种抗癫痫药物在有效浓度范围内男女所占比例汇总分析 283.4.4 2006-2009 年 4 种抗癫痫药物低于浓度范围男女所占比例汇总分析 303.4.5 2006-2009 年 4 种抗癫痫药物高于浓度范围男女所占比例汇总分析 313.5 2006-2009 年 4 种抗癫痫药物测定次数分布情况 334 讨论 34第二部分 环孢素血药浓度监测结果回顾分析1 仪器与试剂 362 方法 362.1 采集血样 36 2.2 测定方法 362.3 血药浓度判断标准 363 结果363.1 20062009 年各年度环孢素 血 药
6、 浓 度 监测分析 373.2 20062009 年四年 内 环 孢 素 血 液 浓 度监测汇总分析 383.3 年龄与环孢素血药浓度监测汇总分析 403.4 不同性别与环孢素血药浓度监测汇总分析 413.5 环孢素监测次数汇总分析 434 讨论 44全文结论45参考文献48致 谢51攻读学位论文期间发表的学术论文52山东大学硕士学位论文5LISTChinese abstract 1English abstract 3Abbreviations 6Introduction 7The first part Retrospective analysis of blood concentration
7、 monitoring of 4 kind anti-epileptic drugs1 Instruments and reagents 92 Methods 92.1 Blood sampling 92.2 Method for determination 92.3 Judgment standard of blood drug concentration 93 Results 93.1 The results of blood concentration monitoring of 4 kind anti-epileptic drugs in each year from 2006 to
8、2009103.1.1 The results of blood concentration monitoring of 4 kind anti-epileptic drugs in 2006103.1.2 The results of blood concentration monitoring of 4 kind anti-epileptic drugs in 2007123.1.3 The results of blood concentration monitoring of 4 kind anti-epileptic drugs in 2008143.1.4 The results
9、of blood concentration monitoring of 4 kind anti-epileptic drugs in 2009163.2 Summary analysis of 4 kind anti-epileptic drugs in each year from 2006 to 2009183.2.1 Summary analysis of 4 kind anti-epileptic drugs in 2006 183.2.2 Summary analysis of 4 kind anti-epileptic drugs in 2007 193.2.3 Summary
10、analysis of 4 kind anti-epileptic drugs in 2008 203.2.4 Summary analysis of 4 kind anti-epileptic drugs in 2009 213.3 Analysis of blood concentration monitoring of 4 kind anti-epileptic drugs from 2006 to 2009223.3.1 Analysis of blood concentration monitoring of valproic acid sodium from 2006 to 200
11、922山东大学硕士学位论文63.3.2 Analysis of blood concentration monitoring of carbamazepine from 2006 to 2009233.3.3 Analysis of blood concentration monitoring of phenobarbital from 2006 to 2009243.3.4 Analysis of blood concentration monitoring of phenytoin sodium from 2006 to 2009253.4 Summary analysis of moni
12、toring person-time, age and sex of 4 kind anti-epileptic drugs from 2006 to 2009263.4.1 The ratio of monitoring person-time of 4 kind anti-epileptic drugs from 2006 to 2009263.4.2 The summary analysis of age using 4 kind anti-epileptic drugs from 2006 to 2009273.4.3 The ratio of male and female in e
13、ffective concentration range of 4 kind anti-epileptic drugs from 2006 to 2009283.4.4 The ratio of male and female lower than effective concentration range of 4 kind anti-epileptic drugs from 2006 to 2009303.4.5 The ratio of male and female more than effective concentration range of 4 kind anti-epile
14、ptic drugs from 2006 to 2009313.5 The distribution of determination frequency of 4 kind anti-epileptic drugs from 2006 to 2009334 Discussion 34The second part Retrospective analysis of blood concentration monitoring of Cyclosporine1Instruments and reagents 362 Methods 362.1Blood sampling 362.2 Metho
15、d for determination 362.3 Judgment standard of blood drug concentration 363 Results 363.1 Analysis of blood concentration monitoring of Cyclosporine in each year from 2006 to 2009373.2 Summary analysis of blood concentration monitoring of Cyclosporine in four years from 2006 to 2009383.3 Summary ana
16、lysis of age and blood concentration monitoring of Cyclosporine403.4 Summary analysis of different sex and blood concentration monitoring of Cyclosporine41山东大学硕士学位论文73.5 Summary analysis of monitoring frequency of Cyclosporine 434 Discussion 44Conclusion 45Reference 48Acknowledgment 51Articles publi
17、shed during postgraduate period 52山东大学硕士学位论文120062009 年山东大学齐鲁医院血药浓度监测回顾性分析2006-2009 qilu hospital of shandong university blood drug concentration monitoring retrospectively研究生 专 业 制药工程导 师 中文摘要摘要：目的：回顾性分析 2006-2009 年所有血药浓度监测情况，以利指导用药。方法：采用回顾性调查分析方法，通过对山东大学齐鲁医院 20062009 年四种主要抗癫痫药血液浓度监测数据进行分类分析。在不同年龄、性
18、别分别汇总低于有效治疗浓度、有效治疗浓度、高于治疗浓度数据。结果：4 种抗癫痫药物中在监测人次上丙戊酸钠所占比例最大（43.41%） ，其次是卡马西平（32.27%） 、苯妥英钠（14.00%） 、苯巴比妥（10.33%） ；4 种抗癫痫药物在 03 岁和 60 岁以上监测人次最少，314 岁监测人次（436 人约占 28.55%）最多；4 种抗癫痫药物男性达有效治疗浓度（31.14%）的比例要远高于女性（12.17%） ，低于有效治疗浓度所占比例男性（29.52%）高于女性（16.43%） ，高于有效治疗浓度所占比例男性（6.33%）高于女性（4.87%） ；4 种抗癫痫药物监测 1 次比例
19、最高（94.26%） ，监测 2 次比例（4.54%） ，监测 3 次以上所占比例极少；4 种抗癫痫药物在有效治疗浓度比较：卡马西平最高（57.97%） ，其次是苯巴比妥（55.26%） 、丙戊酸钠（42.11%） ，苯妥英钠最低（16.41%） 。 1525 例四种抗癫痫药物血药浓度监测结果在有效治疗浓度所占比例为42.94%,低于有效治疗浓度所占比例为 46.79%,高于有效治疗浓度所占比例为10.27%。将环孢素的具体监测结果分为 6 个区段进行比较，结果显示分布于山东大学硕士学位论文2450g/L 的结果仅占总例次的 1.2%3.3%,6.6%9.7%和1.8%7.6%；大部分监测结果
20、分布在 50150g/L，150250g/L，250350g/L 3 个区段，50450g/L 有效浓度范围内的占 91%，各年度监测结果差别意义不大；4346例环孢素监测人次中男性占 3047 次（70.18%） ，女性占 1296 次（29.82%） ，男性的有效治疗浓度内（正常值）所占比例（92.64%）略低于女性（94.21%） ，P0.05 没有差异。5 种药物进行 5833 例次监测,达有效血药浓度的 4670 例次,占总数 80.1%;未达有效血药浓度的 1163 例次,占总数 19.9%;结论： 在应用苯妥英钠、卡马西平、苯巴比妥、丙戊酸钠、环孢素时，应全面分析患者的剂量方案、
21、用药史、重要的实验室数据，结合血药浓度监测结果和临床疗效随时调整剂量，真正做到个体化治疗。临床药师和医师应联合,充分利用 TDM 技术,建立一个长期有效的治疗方案,最大限度保证患者用药安全、有效、经济。关键词:药物监测;血药浓度;回顾性分析2006-2009 QILU HOSPITAL OF SHANDONG UNIVERSITY BLOOD DRUG CONCENTRATION MONITORING RETROSPECTIVELY山东大学硕士学位论文3Postgraduate: SUNGUODDONGMajor: Pharmaceutical EngineeringTutor: GUORUI
22、CHENABSTRACTAbstract: Objective: The blood concentration monitoring from 2006 to 2009 was analysed retrospectively to direct the use of medicine. Methods: The data as name, age, sex and monitoring results were summarized by analysing the blood concentration monitoring data of main anti-epileptic dru
23、gs and cyclosporine which were collected by qilu hospital of shandong university from 2006 to 2009. The data which was lower than effective concentration, equal to effective concentration and more than effective concentration was summarized. Results: Among the monitoring person-time of the 4 kind an
24、ti-epileptic drugs, the largest percentage (43.41%) was valproic acid sodium followed by carbamazepine (32.27%), phenytoin sodium (14.00%) and phenobarbital (10.33%). The monitoring person-time of 4 kind anti-epileptic drugs in the age of 03 and 60 years old was lowest, which was most in the age of
25、314 (436 person). The ratio of male who reached effective concentration of 4 kind anti-epilietic drugs was 31.14%, more than the ratio of female which was 12.17%. The ratio of male whose blood concentration was lower than effective concentration was 29.52%, more than the ratio of female which was 16
26、.43%. The ratio of male whose blood concentration more than effective concentration was 6.33%, more than the ratio of female which was 4.87%. The ratio of monitoring one time was highest which was 94.26%, the ratio of monitoring two times was 4.54%, the ratio of monitoring three times was very low. The ratio of reaching effective concentration of 4 kind anti-epileptic drugs, carbamazepine was highest which was 57.97%, followed by
