目的:分析我院替考拉宁血药浓度监测结果及用药方案特点,为临床合理用药提供参考.方法:收集2017年12月至2018年12月我院使用并监测替考拉宁血药浓度患者的病例资料,回顾性分析替考拉宁治疗方案及血药浓度的分布情况,探讨血药浓度达标与治疗方案的关系及影响因素.结果:214例患者共监测替考拉宁血药浓度357例次,血药浓度达标(>10μg·mL-1)的比例为43.4％.最常用的给药方案为初始每12h给药0.4g,连续3次,其后维持剂量0.4gqd,占43.5％,该方案在治疗早期(2～6d)血药浓度达标率为22.0％.每12 h给药0.4 g,连续5次,维持剂量为0.4 g qd的患者,治疗早期血药浓度达标率为35.6％;治疗初期每12 h给药0.4 g至少3 d的患者,治疗早期血药浓度达标率为68.4％,治疗初期增加替考拉宁日剂量可提高血药浓度达标率.血药浓度达标与肌酐清除率和累计剂量/体重相关(P<0.05).结论:临床中替考拉宁血药浓度达标率低,个体差异大,为保证临床疗效可考虑适当增加替考拉宁的初始给药剂量,监测血药浓度对优化替考拉宁的个体化治疗具有重要的意义.

目的:探讨缺血性脑血管病行介入治疗术患者的CYP2C19基因多态性和临床治疗药物调整之间的关系,寻找应重点进行治疗药物监测和调整的人群.方法:按照纳入排除标准,回顾性收集分析我院2016年8月 –2018年7月入院行神经介入术的缺血性脑血管病患者数据,包括CYP2C19基因检测结果、血栓弹力图ADP抑制率分布、抗血小板治疗方案、缺血性及出血性不良事件.结果:共收集患者数据60例,CYP2C19正常代谢型50.00％(30/60)、中间代谢型43.33％(26/60)、慢代谢型6.67％(4/60);根据血栓弹力图ADP抑制率,氯吡格雷不敏感26.67％(16/60)、低反应性33.33％(20/60)、高反应性5.00％(3/60).共有26.67％(16/60)的患者进行了治疗药物调整.共有11.67％(7/60)的患者在住院期间出现了不良事件,均为缺血性,其中71.43％(5/7)属于氯吡格雷不敏感或低反应性组.结论:临床应对CYP2C19慢代谢型、中间代谢型患者加强药学监护,对于血栓弹力图ADP抑制率显示氯吡格雷不敏感或低反应性患者(<50％)应进行治疗药物调整.

药物临床试验的质量是保护受试者权益和科学评价药物的重要前提.Ⅰ期临床试验是初步的临床药理学及人体安全性评价试验,较Ⅱ/Ⅲ期临床试验全程高风险,如何实现效益-风险最优化一直是被关注的核心问题.针对Ⅰ期临床试验和Ⅰ期临床试验室管理的特点,通过对系统层面和项目层面的风险因素进行识别、评估,提出基于风险的质量管理策略,采取有效措施,全面和持续性降低整个Ⅰ期临床试验周期的风险.

目的 建立液相色谱-串联质谱(LC-MS/MS)法监测感染患者血浆中替加环素浓度.方法 以替加环素-d9为内标,血浆样品用蛋白沉淀法处理,沉淀剂为甲醇.色谱柱为Waters X Select HSS T3 C18柱(2.1 mm ×50 mm,3.5μm),流动相为甲醇-水(含0.1％甲酸v/v),梯度洗脱,流速为0.4 mL·min-1.离子源为MS-ESI,正离子模式,多反应监测(MRM),替加环素和内标的定量离子对分别为m/z 586.3→m/z 513.1,m/z 595.2→m/z 514.2.结果 替加环素在50～2000 ng·mL-1线性关系良好(R2=0.998 4),50,100,500,1600ng·mL-14个质量浓度质控样品的批内精密度(RSD)＜4.56％,批间精密度(RSD)＜7.84％.4例感染患者替加环素谷浓度平均值分别为115.46(48.27 ～ 189.91),245.19(218.17 ～ 294.35),185.40(163.94～206.86),55.87(51.4 ～60.86) ng·mL-1.2例患者鲍曼不动杆菌的抑菌圈分别为12和13mm.结论 该方法准确、快速、灵敏,可用于替加环素血药浓度监测及药代动力学研究.

目的:分析已发表的神经外科术后儿童颅内感染治疗相关文章,探讨目前国内儿童颅内感染治疗现状.方法:检索CNKI数据库自建库以来至2017年12月符合纳入标准的患儿资料,统计颅内感染的致病菌分布、抗菌药物应用及其他治疗和预后等情况,分析国内儿童患者颅内细菌感染的药物治疗方案.结果:CNKI数据库中共检索出11篇关于颅内细菌感染患儿的文献报道,有效病例368例;主要治疗药物包括万古霉素、头孢菌素类、碳青霉烯类等;共121例患者联合鞘内给药;提及治疗效果的有284例,其中治愈188例(66.20％),6例明确有遗留后遗症,多数患者未进行后续随访.结论:儿童颅内细菌感染可使用药物有限,常存在用药不合理、超说明书用药现象,因此需加强药学监护,根据儿童肝肾功能、体重等个体化给药,确保用药安全、有效、经济、合理.

替考拉宁是临床治疗耐甲氧西林金黄色葡萄球菌等耐药革兰阳性菌感染的首选药物之一.本文分别对近年来替考拉宁在老年人、儿童,重症感染、肾功能不全、低白蛋白血症、严重烧伤、血液肿瘤患者等特殊人群中的药动学研究进展进行综述,考察特殊病理生理状态对其疗效和安全性的影响,为临床合理用药提供参考.

目的 总结临床药师参与1例抗感染疗效不佳、高热患者治疗方案调整的过程,为促进临床安全合理用药提供参考.方法 针对1例颅脑手术后反复发热患者,临床药师参与探讨发热原因,排除致热因素,疑为药物热,并针对患者用药情况进行分析,建议调整治疗方案.结果 经调整药物治疗方案,患者体温恢复正常.结论 临床药师应对抗感染治疗进行全程药学监护,对于抗感染治疗中仍有发热的患者,应综合考虑,避免药物热等不良反应的发生,以促进临床合理用药,保证患者用药安全.

目的 探讨临床药师快速融入医疗团队进而有效开展临床药学工作的方法.方法 结合国内现有临床药师相关文件,以及我院临床药师工作经验,分层次探讨临床药师如何快速融入医疗团队中并有效发挥其作用.结果 临床在药品不良反应、特殊人群用药、治疗方案个体化调整等方面对药师工作存在需求,临床药师需要建立与医生接轨的临床思维,从切入点着手融入临床工作.部分医院缺乏规范化管理,无法保障临床药师顺利开展工作.结论 药师应通过提升业务水平,建立工作思维,与医疗团队建立互补且互需的关系.医院应在管理水平上完善临床药师工作制度以促进临床药师与医疗团队的融合.

目的:探讨在早期药物心脏安全性评价中基于风险浓度-QTc(concentration-QTc,C-QTc)的研究策略.方法:参考ICH-E14全面QT研究(thorough QT study,TQT研究)指南和FDA“白皮书”指导原则,结合既往实际开展TQT研究及C-QTc研究经验,探讨应用C-QTc研究评估药物心脏安全性研究策略.结果:本文探讨了C-QTc研究代替TQT研究对候选药物进行心脏安全性评价的方法,并对C-QTc研究的适用范围、受试人群选择、样本量、剂量设计、组别设计、心电图数据采集、C-QTc模型建立及评价、结果判定及安全预案进行分析及阐述.结论:前期基于风险的充分设计考虑是成功开展以C-QTc模型评价新药心脏安全性的基础,对豁免开展TQT研究具有重要意义.

目的:通过监测重症感染患者负荷剂量替考拉宁血药谷浓度,分析药物谷浓度分布情况、达标率、影响因素及临床疗效和安全性,为合理用药提供参考.方法:选取2017年12月至2018年4月解放军总医院重症医学科收治的疑似或确诊多重耐药革兰阳性菌(G+)感染患者共40例,根据负荷天数不同分为A组(3d,n=22)和B组(4d,n=18),给予替考拉宁每12 h 400 mg,之后以400 mg·d-1维持,分别于首次维持剂量给药前30 min测定替考拉宁血药谷浓度(Cmin);同时测定用药过程中患者肝、肾功能相关指标,记录其不良反应.结果:Cmin＞ 10 mg·L-1总达标率为65％.A、B2组达标率分别为50.0％和83.3％,差异有统计学意义(P＜0.05).除肌酐清除率(Ccr)外,其余因素对C min无影响.临床好转率95％,用药过程中未出现急性肝、肾损伤.结论:重症感染患者替考拉宁血药浓度随负荷剂量天数增加,血药谷浓度达标率及临床好转率升高,临床用药安全性好.

随着科学技术尤其是生物技术的发展,生物技术药物在一些临床治疗领域显示出其他药物无法替代的作用,在全球医药市场中占比也不断提高,并且大批原研生物药将在2020年专利到期,生物类似药迎来重要的发展机遇.有机构预测,未来10年,全球生物类似药市场将增长数十倍.因此,生物类似药的开发受到许多国家重视,欧洲、美国、日本等主要发达国家和组织相继出台了系列相关的指导原则,以期抓住生物类似药的发展机遇.我国也于2015年颁布了《生物类似药研发与评价技术指导原则(试行)》.本文主要从临床药理学、参照药选择、临床有效性、安全性和临床适应证外推等方面对比分析国内外生物类似药临床研究指导原则,以期对我国生物类似药临床研究提供借鉴和参考.

Objective: To establish a high-performance liquid chromatographic (HPLC) method for the concentration determination of levetiracetam in human plasma. Methods: With metronidazole as the internal standard, acetonitrile was added to plasma sample for precipitating protein. The supernatant was washed with dichloromethane, and the upper aqueous was injected to HPLC. Hypersil BDS column (4.6 mm × 250 mm, 5 μm) was selected. And the mobile phase was a mixture of water and acetonitrile (87 : 13, v/v) at a flow rate of 1.0 mL·min-1. The detection wavelength was 205 nm. Column temperature was 40 ℃ and injection volume was 20 μL. Results: Levetiracetam showed a good linear relation in the range of 2.5 – 80.0 μg·mL-1with a good correlation coefficient (r = 0.999?4). The intra-batch variations were ranged from 1.06% to 1.97% and inter-batch variations were ranged from 3.46% to 8.14%. The mean recoveries were ranged from 94.00% to 102.48%. Conclusion: The method was sensitive, specific and simple. It is suitable for monitoring the concentration of levetiracetam in human plasma.

Objective: To analyze the literature related to the clinical research of etimicin at the time of etimicin listed in China for 20 years, so as to provide references for clinical rational drug use. Methods: Based on the methods of bibliometrics, the relevant literature on the clinical research of etimicin were collected and summarized. Statistical analysis was carried out in terms of the publication date, languages, journals, types of literature, types of clinical infection, adverse reactions and incompatibility. Results: A total of 527 literature were included. The domestic research was dominant among the related literature, most of which were published in Chinese journals (374 journals, 98.9%). Clinical research of etimicin mainly focused on respiratory infection (86 studies, 57.7%). ADR research of etimicin mainly focused on ototoxicity and nephrotoxicity (38 studies, 52.1%), and the incompatibility of etimicin with cephalosporins was reported in 38 articles, which accounted for 40.4% among enrolled studies. Conclusion: As a self-developed aminoglycoside antibiotic in China, etimicin had a wide range of clinical applications and a lower incidence of adverse reactions than similar varieties. It is of great significance to further study and explore etimicin for the prevention and treatment of infectious diseases.

Objective:This study was designed to investigate the current practice of skin testing (ST) for betalactams in Chinese hospitals and discuss the potential problems by questionnaires.Methods:A fourteen-question questionnaire was sent to one hundred hospitals which employed professional clinical pharmacists in Mainland China and then collected back via e-mail or fax.The questions included the information of hospitals,detail information of ST practice,the clinical choices for patients who had an allergic history of beta-lactams and also the concerns of ST for oral penicillin preparation.Results:The total response rate was 80％.The current practice of ST for beta-lactams performed in Chinese hospitals differed with regard to the technique,reagent,test concentration,injection volume and positive criterion.The respondents' attitudes for patients' allergic history and oral penicillin preparation testing were also inconsistent and varied.Conclusion:There was still a lack of unified standard of ST for beta-lactams in Chinese Hospitals.This survey highlighted an urgent need for national guideline or consensus of ST for beta-lactams to increase using safety and normativity for these antibiotics in China.

Objective: To investigate the effect of intervention by clinical pharmacists in vancomycin application. Methods:Data of vancomycin therapeutic drug monitoring (TDM) was collected from September 2016 to August 2017 in our neurosurgery department. Compliance rate, timeliness, medication rationality, treatment effect, and result of vancomycin TDM before and after clinical pharmacist's intervention were analyzed. Results: The quantity (before intervention 43 cases, after intervention 92 cases) and timeliness (before intervention 4.87 ± 3.78 d, after intervention 3.23 ± 2.51 d) of vancomycin TDM were improved after the intervention of clinical pharmacists. The course of therapy was shortened by pharmaceutical intervention (before intervention 10.98 ± 10.18 d, after intervention 10.92 ± 7.15 d) while the compliance rate of vancomycin concentration was not risen after intervention. The compliance rate of vancomycin concentration was more correlated with the regimen. Conclusion: The intervention of clinical pharmacists could promote the rational use of medication and improve the treatment efficacy.

目的:分析氟比洛芬酯相关性肝损害的临床特点及风险因素.方法:利用"医疗机构ADE自动监测与智能评估警示系统"(ADE-ASAS),回顾性监测我院2017年使用氟比洛芬酯的住院患者相关肝损害发生情况,自动筛选纳入病例,人工评价其关联性、ADR发生率、风险因素,总结发生特征.结果:氟比洛芬酯致肝损害发生率为3.00％,损伤程度以轻度为主,损伤类型主要表现为肝脏生化学检查异常,相关风险因素为性别及用药时长(P<0.05),男性发生率显著低于女性(OR=0.652,95％CI:0.465–0.915),用药时长与其正相关(≤1 d:OR=0.353,95％CI:0.233–0.559;2～7 d:OR=0.362,95％CI:0.235–0.556;>7 d:OR=1),ADR平均发生时间为用药后的(5.40±4.06)d.结论:氟比洛芬酯导致肝损害的发生率较为常见,多为轻度,临床用药中对于女性患者、用药时间较长的患者应更加关注其肝功能变化.利用专项软件实施ADR监测准确高效,以低成本付出实现高质量研究,可辅助药师开展药品上市后安全性评价,降低用药风险.

目的:探讨临床药师在颅咽管瘤术后患者中进行药学监护的作用.方法:针对中国人民解放军总医院神经外科2016年5月至2017年6月期间27名颅咽管瘤切除术患者围手术期常见的并发症,结合实际病例,分析临床药师进行药物治疗建议、药学监护及对患者用药教育等工作的价值.结果:临床药师结合患者实际情况,进行全程药学监护和用药教育,提高了患者的治疗效果.结论:临床药师对颅咽管瘤术后患者中进行药学监护有利于提高患者的预后,具有重要意义.

目的 评估医院住院患者应用替加环素的病例特点和用药情况,为临床优化使用替加环素给药方案提供参考.方法 基于"医疗机构ADE主动监测与智能评估警示系统",对医院2012年3月1日-2017年3月31使用过替加环素的住院患者进行回顾性分析,收集患者的年龄 、性别 、身高 、体质量 、科室分布等基本资料,评估抗感染疗效及药品不良反应等病例特点以及用药适应证 、给药剂量 、途径 、溶媒 、疗程等用药行为.结果 共499例住院患者应用替加环素抗感染治疗,平均年龄(64.29±20.52)岁.抗感染用药原因中仅169例次(30.18％)符合说明书批准的适应证;首剂给予负荷剂量的为252例(50.50％),137例(27.45％)的维持剂量为100 mg,q12h,高于说明书推荐剂量;替加环素给药前微生物送检率为66.93％;抗感染治疗有效率为41.88％;病历记载的ADR共11例 、通过系统主动监测的药源性肝损伤为8例,未发现药源性胰腺炎病例.结论 医院住院患者应用替加环素存在微生物送检率未达标 、超适应证 、超剂量使用以及部分病例未给予首剂负荷剂量等问题,提示临床应规范微生物标本送检并优化替加环素给药方案.

目的 分析国内外关于伏立康唑治疗药物监测(TDM)的文献资料,为临床合理用药提供参考.方法 在PubMed、EmBase、SCI、中国知网和万方数据库中检索全部相关文献,对纳入研究文献的发表年份、作者及研究机构、文章类型、引频、期刊等进行统计分析.结果 共纳入295篇相关文献,其中英文265篇,中文30篇.伏立康唑血药浓度监测研究热点主要为监测方法、血药浓度与基因关系、血药浓度与药物不良反应关系.结论 伏立康唑是临床抗真菌治疗中的重要选择之一,由于影响伏立康唑药代动力学的因素较多,开展伏立康唑TDM及基因型检测对提高临床疗效,降低药物不良反应具有重大意义.

Objective To evaluate the association between flurbiprofen axetil and liver damage in clinical use. Methods Taking flurbiprofen (axetil) as subject terms, and adverse drug reactions, hepatotoxicity, hepatic damage, transaminases and hyperbilirubin as search term, the authors collected literatures from CNKI, WANFANG Medical Database, VIP Database, Pubmed, Medline and Cochrane CENTRAL Database published at home and abroad from January 1980 to November 2017. The literatures were read and screened for the ADR case reports and drug safety research reports into the study. Data record sheets was designed and the basic information, method feature and intervention were picked up and recorded. Using descriptive research method, the authors evaluated the probability, extent and type of liver damage caused by flurbiprofen (axetil). Results There were 3 randomized trials studies, 1 prescription statistic study, 1 case statistic study and 3 individual case data studies in 8 papers screened. By analyzing 1210 patients in 3 randomized trials studies, the authors found that about 1% of patients have abnormal liver function. Then they concluded that flurbiprofen (axetil)-induced liver damage was not an uncommon adverse effect. 6 literatures recorded abnormal indicators of liver function without the changes of the bilirubin index. 5 of them indicated abnormal transaminase index and 2 of them indicated abnormal alkaline phosphatase index. The degree of liver damage is judged to be mild and abnormal transaminase to be the main type of liver injury. Conclusion The authors think that flurbiprofen (axetil)-induced liver damage is a common adverse effect and the degree of injury is mainly mild and abnormal transaminase is judged as the main type of liver injury. Considering the limited number and poor quality of current literatures, the relationship between flurbiprofen (axetil) and liver damage needs further study with more clinical statistical analysis in the authors' hospitals.