目的 分析阿来替尼药物不良反应(adverse drug reactions,ADRs)的发生规律,为临床合理用药提供文献依据.方法 检索截止到2022年2月中国知网数据库(CNKI)、万方、维普及Pubmed、Medline等数据库关于阿来替尼的文献.对文献进行整理,分析文献发表的分布情况,并对其不良反应发生时间、累及系统、临床表现及转归等信息进行分析汇总.结果 共纳入文献28篇,个案32例.首次发表关于阿来替尼ADRs的个案报道是2015年.患者中男性12例,女性20例,平均年龄为(62.9±10.5)岁.所致ADRs主要累及呼吸系统(28.2％),其次为消化系统、皮肤、泌尿系统等.结论 阿来替尼在用药的过程中要加强监测,做好跟踪随访和记录,发现ADRs及时处理,避免病情加重.

目的 探讨鼠类肉瘤滤过性毒菌致癌基因同源体B1(v-Raf murine sarcoma viral oncogene homolog B1,BRAF)V600E阳性突变的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者治疗方案的疗效和安全性,为该类患者的药学监护提供参考.方法 分析天津医科大学肿瘤医院2018-2019年收治的2例BRAFV600E阳性突变的晚期NSCLC患者,结合患者疾病变化及诊疗指南对治疗方案进行评估,以药物使用方法、用药教育及不良反应监测为切入点,为BR4F阳性突变的晚期NSCLC患者实施药学监护,并协助临床医师及时处理相关不良反应.结果 2例BRAF V600E突变的晚期NSCLC患者在接受BRAF、丝裂原活化的细胞外信号调节激酶抑制剂联合治疗后均显示出一定的抗肿瘤活性,且不良反应均在可控范围.结论 临床药师通过药学监护可促进临床合理用药,保障患者用药的安全性和有效性.

Kidney cancer usually requires multidisciplinary individualized treatments. No matter what kind of treatment, drugs are essential. According to the "six-step process" (prescription legitimacy review, patient basic information evaluation review, treatment protocol review, organ function and laboratory index review, pretreatment review, and unconventional prescription review) in prescription review proposed by the anti-tumor drug prescription review expert group and referring to domestic and foreign kidney cancer guidelines and drug instructions in recent years, this consensus selects 9 targeted drugs and 4 immunotherapeutic drugs that are currently commonly used in China and elaborates the key review points in patient basic information evaluation review, treatment protocol review, and organ function and laboratory index review of kidney cancer drug treatment, in order to provide reference for clinical front-line pharmacists to review prescriptions of kidney cancer patients and promote rational drug use in clinic.

目的 基于网络药理学和分子对接技术分析四物汤抗乳腺癌的作用机制.方法 通过中药系统药理学数据库分析平台(TCMSP)获取熟地黄、白芍、川芎、当归的主要活性成分及其靶点,根据吸收、分布、代谢和排泄(absorption、distribution,metabolism and excretion,ADME)筛选中药活性组分;通过在线人类孟德尔遗传数据库(OMIM)、治疗靶标数据库(TTD)、Genecards和Drugbank数据库获取乳腺癌主要作用靶点;通过Venn Diagram得到四物汤与乳腺癌的共同靶点;利用BiosoGenet进行蛋白质-蛋白质相互作用(protein-protein interaction network,PPI)分析,构建PPI网络;采用Metascape平台分析"药物-成分-靶点"及其参与的生物过程及通路,采用Cytoscape3.8.0软件构建"活性成分-疾病-通路"网络,并运用AutoDock及Pymol对关键靶点与相应活性成分进行分子对接验证.结果 从四物汤中筛选得到40种活性成分及147个作用靶点,与1505个乳腺癌相关靶点取交集,得到61个共同靶点;四物汤抗乳腺癌的核心活性成分为山柰酚、β-谷甾醇、没食子酸、豆甾醇等,关键靶点为前列腺素 G/H 合酶2(prostaglandin G/H synthase 2,PTGS2)、雌激素受体(estrogen receptorl,ESR1)、RAC-a丝氨酸/苏氨酸-蛋白激酶(RAC-alpha serine/threonine-protein kinase,AKT1)等;四物汤抗乳腺癌的生物学通路众多,主要功能为调控细胞周期进程、血管生成、激素水平等.分子对接结果显示,筛选的主要活性成分与其对应靶蛋白均具有较好的结合活性.结论 四物汤抗乳腺癌具有多成分、多靶点、多通路的特点,为其临床应用提供基础.

目的 分析2017年1月—2019年12月天津市肿瘤医院(天津医科大学肿瘤医院)抗肿瘤分子靶向药使用情况,为临床合理用药及抗肿瘤新药研发提供参考.方法 收集天津市肿瘤医院2017年1月—2019年12月期间抗肿瘤分子靶向药品种/品规数、使用金额、在抗肿瘤药使用金额中的构成比,并对用药频度(DDDs)、限定日费用(DDC)及排序比(B/A)进行回顾性分析.结果 2017—2019年,本院抗肿瘤分子靶向药品由11种增至30余种;使用金额及在抗肿瘤药使用金额中的构成比呈逐年快速增长趋势,3年来使用金额由0.28亿元增长至3.65亿元,增加了12倍多,构成比从9.31％增至41.57％;各抗肿瘤分子靶向药DDDs也大幅增加,其中以贝伐珠单抗、曲妥珠单抗增幅居前列;而DDC逐年下降,降幅大于25％,随之,多数药物B/A值逐渐接近或大于1,使用金额与DDDs趋于一致.结论 本院抗肿瘤分子靶向药物使用与本院收治患者人群特征和指南治疗方案基本一致,使用基本合理;医改新政策出台,分子靶向药纳入医保,药品价格大幅下降,患者治疗费用降低,使得更多患者的治疗与国际接轨,提高了治疗的有效率,成为新医改政策的直接受益者.

目的 分析替格瑞洛药物不良反应(ADRs)的发生和分布的一般规律,为临床合理用药提供依据.方法 检索截至2018-10-31中国医院知识总库、维普、万方及PubMed、EMbase等数据库中关于替格瑞洛ADRs的文献.用Endnote软件及人工方法进行整理,分析文献发表的分布情况,并对ADRs发生类型和程度等信息进行分析汇总.结果 共纳入文献32篇.首次发表关于替格瑞洛ADRs的文献是在2012年.涉及替格瑞洛引起ADRs主要为呼吸系统、消化系统、皮肤和皮下组织等.结论 替格瑞洛在用药的过程中要加强监测,做好跟踪随访和记录,发现ADRs及时处理,避免病情加重.

近年来,程序性死亡受体-1(programmed cell death-1,PD-1)抑制剂派姆单抗(Pembrolizumab)在非小细胞肺癌(non-small cell lung cancer,NSCLC)的治疗中显示出良好的疗效.2015年10月,派姆单抗获得美国FDA快速审批,用于治疗程序性死亡配体-1 (programmed cell death-L1,PD-L1)阳性且在其他治疗后疾病进展的转移性NSCLC.随着临床试验的开展,派姆单抗在NSCLC治疗中的适用范围逐渐扩大,本文对派姆单抗治疗NSCLC的临床研究现状进行综述.

目的 探讨临床药师参与抗肿瘤用药会诊的切入点,为其参与肿瘤多学科诊疗模式提供参考.方法 临床药师通过参与3例抗肿瘤用药会诊的实践,包括来曲唑与氨氯地平药物相互作用、环磷酰胺诱导低钠血症和肌酐异常患者卡铂剂量计算,协助医师对疑难问题展开分析并提出治疗建议.结果 来曲唑与氨氯地平相互作用可能导致肝酶异常升高,环磷酰胺可通过抗利尿激素分泌异常综合征机制来诱发低钠血症,低血肌酐患者应用Calvert公式计算卡铂剂量可能存在潜在风险.结论 肿瘤科临床药师可以利用对药物相互作用、不良反应评价和药物剂量调整等药学专业方面的优势,在肿瘤多学科诊疗模式中发挥积极作用.

OBJECTIVE To evaluate the incidence and risk factors for severe neutropenia in breast cancer patients receiving taxanes and epirubicin (TE) combination chemotherapy.METHODS Retrospective analysis was performed for breast cancer patients receiving TE combination regimen for neoadjuvant or systemic chemotherapy from 2014 to 2015 in Tianjin Medical University Cancer Institute and Hospital.Patients' data of physiology,pathology,medications and the results of neutropenia were collected,and risk factors of severe neutropenia were analyzed by logistic regression.RESULTS Totally 126 patients were analyzed in this study,50 patients (39.7％) developed severe neutropenia during chemotherapy,and 45 (35.7％) patients developed after the first cycle treatment.Among these factors,paclitaxel liposome as the taxane (OR =5.84,P =0.003)and higher dose intensity of epirubicin (OR =1.11,P =0.001) were found to be associated with a higher risk of severe neutropenia.CONCLUSION Chinese breast cancer patients are at relatively high risks of severe neutropenia when receiving TE regimen chemotherapy,paclitaxel liposome and higher dose intensity of epirubicin may increase the risk.

Objective:Investigate the clinical applications of bevacizumab in our hospital,in order to remind and improve the rational use of non-formulary patients' own medicines.Methods:Retrospective analyse patients whose orders include "bevacizumab" from June 2014 to May 2015 in our hospital.The statistical medication data and adverse reactions were recorded,and the rationality and safety of clinical application were evaluated according to the latest Chinese and English instructions,guidelines and other clinical data.Results:A total of 151 patients used bevacizumab were collected,of which 133 (88.1％) diagnosis were in accordance with the indications of the instructions or recommend guildlines.There were off-label uses on dose (45.7％),route of administration (5.6％),solvent (26.5％),pretreatment (78.8％) and postoperative interval (1.3％).The primary adverse reactions were mostly related to the combining chemotherapy.Few and mild side effects were observed during single use of bevacizumab.New side effects,including 2 cases of hypercholesterolemia and 2 cases of fatty liver,were observed.Conclusion:Most of the clinical applications of bevacizumab in our hospital comformed to the instructions and guidlines.However,off-label uses were still existed.Hospital administrators and clinical pharmacists should make efforts to strengthen the management and standardization of non-formulary anticancer agents,and make continuous monitoring on post-marketing drugs with new added indications.

Objective:To explore the role of clinical pharmacists in pharmaceutical care for a patient with febrile neutropenia after chemotherapy.Methods: According to the guidelines,such as "Antimicrobial Clinical Application in Patients with Fever and Neutropenia: A Chinese Guideline in 2012","Antimicrobial Prophylaxis and Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology Clinical Practice Guideline" and "2006 Update of Recommendations for the Use of White Blood Cell Growth Factors: An Evidence-Based Clinical Practice Guideline", the service provided by clinical pharmacists in the course from diagnosis till the whole treatment in a patient with of lung cancer and chemotherapy-induced febrile neutropenia was followed and analyzed.Results: Clinical pharmacists performed pharmaceutical care in chemotherapy drug selection and adjustment, diagnosis and treatment process of bone marrow suppression, antimicrobial selection and application and et al.Conclusions:Clinical pharmacists can play a positive role in promoting the rational use of drugs, helping physician make individualizde regimens and others.

Objective To investigate the utilization of breast cancer endocrine therapy drugs in Tianjin Cancer Hospital from 2011 to 2016. Methods The utilization information of breast cancer endocrine therapy drugs in Tianjin Cancer Hospital from 2011 to 2016 was extracted, and the consumption sum of drugs, defined daily doses (DDDs), defined daily cost (DDC), and drug sequence ratio (B/A) were analyzed statistically. Results From 2011 to 2016, clinical application of endocrine therapy for breast cancer increased year by year. The proportion of AIs was more than 70%. DDDs of various drugs also showed an overall trend, while ethoxetron (import) increased the most. DDC values of all kinds of drugs were steadily lower. Most of the breast cancer endocrine therapy drugs B/A was close to 1.00, indicating that the synchronism was better. Conclusion The utilization of breast cancer endocrine therapy in Tianjin Cancer Hospital is reasonable, according with the principle of safety, effectiveness, economy, and convenience.

目的:了解我院药品不良反应(ADR)发生的特点及一般规律,为临床合理用药提供参考。方法:统计我院2007～2009年上报的154例ADR报告中患者的基本情况,以及涉及药物品种、给药途径、临床表现等。结果:药品不良反应报告中女性构成比略高于男性,50岁以上患者发生ADR比例较高;引起ADR最常见的药物为抗肿瘤药和免疫调节药,其次为中药制剂;累及的器官-系统以皮肤及附件损害最为常见,其次为全身性损害和心血管系统损害。结论:应及时准确地ADR监测上报、分析评价信息回馈临床,以预防和减少ADR的发生,保证药物治疗的安全有效。

目的探讨临床药师参与肿瘤内科的工作流程。方法通过培训学习,探索适合临床应用的工作方法。结果临床药学工作应从患者、医师、护士3个途径同时开展。结论临床药师需通过适宜的工作流程,完善患者的药物治疗。

Objective:To investigate the distribution of Ursolic Acid Phospholipid Nanoparticles(UA-PL-NP) in mice.Methods:Kunming mice were injected UA-PL-NA through caudal veins,and the plasma and the main tissues of these mice were collected at 5 min,1 h and 4 h after injection,respectively.RP-HPLC method was used to determine the concentrations of UA in the plasma and the main tissues.Results:(1) UA mainly distributed in liver and gastrointestinal tissues.(2) A linear increase was noted with increasing concentrations of UA in the main tissues.(3) UA concentration decreased rapidly in gas-trointestinal tissue,and only an extremely low concentration was remained at 4 h after injection.UA concentration in liver in-creased constantly after injection,and even at 4 h after injection,it maintained a high level [(52.15±18.61) mg·kg-1].Conclu-sion:UA-PL-NP distributes quickly in liver and gastrointestinal tissues on the early stage of injection.After administration,UA concentration in gastrointestinal tissues releases into blood and the redistribution reaches balance.In this way,a high-concentration of UA maintains in liver tissue.UA-PL-NP has a good hepatic targeting distribution characteristic in mice.

目的:观察注射用纳米羟基喜树碱(HCPT纳米针)静脉推注后在家免血浆药物浓度随时间变化趋势和药动学参数以及小鼠体组织分布特征.方法:建立HPLC检测家兔血浆和小鼠各组织中羟基喜树碱含量的方法;绘制3个剂量组(2.5、5.0、7.5mg/kg)家免血浆药-时曲线并采用3p97软件模拟房室模型并计算药动学参数;BALB/c小鼠给予HCPT纳米针(10mg/kg)后,检测15min、1h和2h各组织和血浆中羟基喜树碱的含量.结果:1)HCPT纳米针家免耳静脉单次给药符合1/C2权重的三室模型,AUC和Vd等药动学参数在既定药物浓度范围内呈线性改变.2)HCPT纳米针在肝组织中浓度最高,分布顺序:肝＞肾＞脾＞肠＞胃＞肺＞心.3)HCPT纳米针给药后在肝组织保留时间长.结论:HCPT纳米针在肝组织中药物浓度高、存留时间长,具有明确的靶向性.

AIM: To investigate the pharmacokinetics (PK) of 10-hydroxycamptothec (HCPT) nanoparticle injection iv by comparing with the HCPT common injection in rabbits. METHODS: HCPT in plasma were quantitated by reversed-phase HPLC and UV detector. 3p97 software was used in calculation of compartment model and PK parameters. RESULTS: The concentration-time profile of HCPT nanoparticle injection was best described by three-compartment model, and the common injection was described by two-compartment model. Plasma peak concentration (C_ max) of HCPT common injection was three times as many as that of nanoparticle injection in equal dosage. Area under curve (AUC) of HCPT common injection was twofold higher than that of nanoparticle injection. Apparent volume of distribution of central compartment (V_c) of HCPT nanoparticle injection was greater than that of nanoparticle injection in equal dosage. HCPT nanoparticle injection had a longer elimination half life (T_ 1/2β) than that of common injection. CONCLUSIOM: The blood drug concentration and PK characteristic of HCPT nanoparticle injection were very different from HCPT common injection in rabbits.

AIM: To investigate the tissue distribution performance of 10-hydroxycamptothecin(HCPT) nanoparticle injection in mice and those of HCPT nanoparticle injection's peculiar tissue distribu-tion transformation in mice by comparing with control substance——HCPT common injection. METHODS: HCPT(nanoparticle or lyophilized injection) was administered to BALB/c mice by bolus injection at dose of 10 mg·kg -1 body weight. Drug levels in various tissues were detected by HPLC and UV detector at 15, 60 and 120 min after injection. Characteristics of tissue distribution were contrasted between different dosages and sample forms. RESULTS: (1) The highest concentration of HCPT nanoparticle injection was obtained in liver. And the sequence of HCPT levels in various tissues was: liverkidneyspleenstomachlungheart.(2) Concentration of nanoparticle injection were higher than lyophilized form in several kinds tissues (e.g. liver, spleen, lung, kidney, stomach). Especially in liver, HCPT nanoparticle injection reached 37.66 times of the common form. (3) HCPT nanoparticle injection prolonged obviously accumulated in liver, while no conspicuous visible accumulated organs in common form group. CONCLUSION: Comparing with common forms, HCPT nanoparticle injection could distribute into organs more extensively and reflect great liver targeting capability.