抗结核药物固定剂量复合制剂推广应用的SWOT分析

结核病是一种严重危害人类健康的慢性传染病。当前,我国结核病疫情又出现恶化和回头的趋势。我国结核病患者服药量多,剂型大,服药方法繁锁也是患者服药依从性低、不易完成正规化疗的重要因素。因此开发服用简便、新型抗结核药具有举足轻重的现实意义。固定复合制剂(fixed-dosecm-bination,FDC)是WHO推荐和推广使用的药剂,具有简化处方、减少药物滥用、方便服药、提高患者依从性和耐药发生率等多方面的好处。SWOT分析是优势(strengths)、劣势(weakness)、机遇(oppor-     

抗结核固定剂量复方制剂有关物质的测定

建立了高效液相色谱法测定抗结核固定剂量复方制剂(FDC)品种异福片、异福酰胺片及乙胺吡嗪利福异烟片中的有关物质.采用C18色谱柱,以0.01 mol/L磷酸盐缓冲液-甲醇(40∶60)为流动相,检测波长254 nm.经专属性试验、系统适用性试验、耐用性试验和溶液稳定性试验证实方法可行,增加有关物质的测定方法有利于其复方制剂药品质量的控制.     

抗结核固定剂量复合制剂

抗结核药物的固定剂量复合制剂体现了80年代抗结核治疗的重要进展。它是将数种不同的抗结核药按一定的剂量比例混合制成的复方制剂。剂型有胶囊、片剂。按其组成药物可分三联药(由异菸肼、利福平、吡嗪酰胺组成)和二联药(由异菸肼、利福平组成)。目前几种常用的复合制剂的类型及组成见表1。     

抗结核药物固定剂量复方制剂开发与评价的基本考虑

结合审评实践中发现的问题，初步探讨开发与评价抗结核药物复方制剂临床研究应考虑的问题。     

抗结核固定复合制剂药物不良反应观察

目的 观察抗结核固定复合制剂药物不良反应.方法 选取2018年10月-2019年10月辽宁省本溪市疾病预防控制中心收集的结核病患者300例,采用随机数字分配的方式分为观察组、对照1组及对照2组,每组100例.观察组采用固定复合制剂,对照1组采用固定复合剂3联药物,对照2组采用板式组合药物.观察所有患者治疗不同时间不良反...     

436例肺结核患者抗结核固定剂量复合制剂应用影响因素分析

目的 探讨江西省结核病医疗机构抗结核固定剂量复合制剂（FDC）使用情况及影响因素,为全省推广应用制定相应对策提供参考依据。方法 选择江西省胸科医院2021年4～7月登记的436例新诊断的利福平敏感或耐药未知肺结核患者作为研究对象,采用定量和定性相结合的方法对其使用FDC影响因素进行分析。结果 436例患者中,347例（79.59%）接受FDC治疗,其中207例（59.65%）完成疗程或治愈,不良反应91例（20.87%）。单因素分析,是否接受抗结核病固定复合剂治疗在年龄、职业、文化程度、婚姻状况、诊断结果方面差异有统计学意义（P值均<0.05）;多因素Logistic分析职业和文化程度是是否接受FDC抗结核药品的独立风险因素。结论 抗结核固定剂量复合制剂适合在初治活动性肺结核、初诊利福平敏感或耐药未知肺结核患者中应用;应加强FDC抗结核药品的早期药物不良反应的监测,及加强患者和医务人员的健康科普和培训。     

抗击结核病第三次回潮的有效药物——复方抗结核制剂

1 概况 结核病是一种常见、多发的慢性传染病,在和平环境中结核病控制工作已取得显著成效。近几年,结核病在世界上第三次回潮,深受各国的关注。据1993年WHO发布的疾病动态报告预测,1995年全球死于肺结核病的总数接近300万;因传染病死亡的青、壮年中,结核病占其中一半。我国卫生防疫司预测,全国活动性肺结核病人约有600万,涂阳患病率为134/10万,每年死亡23万人左右,是其它传染病死亡总数的2倍。上海虽是全国结核病发病率最低的地区,但每年仍约有5000例新发病例,其中痰菌阳性的约为2000人左右。     

抗结核固定剂量复合制剂在结核病治疗环节存在的不良反应分析

目的:研究抗结核固定剂量复合制剂在结核病预防治疗期间应用所致不良反应情况,为临床合理用药提供参考.方法:回顾性分析在我中心药房登记领药的应用抗结核固定剂量复合制剂治疗的1220例患者临床资料,统计不良反应发生情况,回顾治疗效果.结果:1220例患者共108例发生不良反应,不良反应发生率为8.85％.不良反应均为单发,发病率从高到低依次为:胃肠反应、肝功能损害、血色素降低、皮肤过敏、关节疼痛.81例在强化期出现不良反应,占比75.00％;27例发生于巩固期,占比25.00％;8例停药,1例转为耐多药治疗,其他患者经对症处理不良反应消失.总体分析,1220例患者临床治愈率96.89％,失败率2.86％,死亡率0.25％.结论:抗结核固定剂量复合制剂对结核病有显著治疗效果,但应用中容易引发不良反应,尤其以胃肠反应及肝功能损害最为常见.临床应展开用药知识宣传及用药监测,提高结核病的治疗效果及患者用药依从性.     

8369例抗结核固定剂量复合制剂应用情况分析

目的分析和评价宝鸡市2015—2019年肺结核患者使用抗结核固定剂量复合制剂(FDC)情况和治疗效果。为进一步做好结核病治疗、管理工作提供科学依据。方法以中国结核病管理信息系统、结核病专报系统的结核病患者数据为基础,结合结核病季度报表、药品报表等,对全市12个县(区)结核病管理系统登记的初、复治肺结核患者FDC的使用、治疗效果及不良反应等进行分析比较。结果5年间,宝鸡市结核病管理系统登记的患者共8968例,8369例使用了FDC,占93.3%。2033例病原学阳性患者中,1843例全疗程使用FDC治疗,治愈1699例,治愈率92.1%。肺结核患者数呈现平稳下降趋势,差异有统计学意义(χ^(2)=975.493,P<0.05)。病原学阳性患者FDC使用情况逐年提升,差异有统计学意义(χ^(2)=948.431,P<0.05)。结论抗结核固定剂量复合制剂应用效果肯定。     

固定剂量药物复方治疗结核病

随着获得性免疫缺陷综合征(AIDS）的流行。结核病（TB)在全球范围内死灰复燃。固定剂量药物复方(FDC)治疗TB大大方便了患者,提高了治疗依从性。为有效控制TB提供了保证。     

Use of fixed-dose combination drugs for the treatment of glaucoma

Glaucoma is a leading cause of irreversible visual loss. This potentially blinding disease is a progressive optic neuropathy associated with elevated intraocular pressure (IOP). Initial therapy for glaucoma typically consists of topical medications or laser treatment to lower IOP. Frequently, more than one medication is required to achieve adequate control of IOP. However, more medications means more bottles and greater complexity for the patient. There are several potential benefits of fixed combination medications compared with using the individual components separately. These include a reduction in the total number of drops and preservative instilled per day, cost savings, improved tolerability and compliance and avoiding the washout effect resulting from rapid-sequence instillation of multiple drops. Attempts to develop effective fixed combinations of glaucoma medications date back several decades. In recent years, fixed combinations of commonly paired drugs have been approved by various regulatory bodies in different countries and have gained wide acceptance. Current commercially available, fixed combination drugs include the topical beta-adrenoceptor antagonist timolol 0.5% combined with a prostaglandin, a topical carbonic anhydrase inhibitor or an alpha-adrenoceptor agonist. Although there is no uniformity among registration trial designs, most published literature compares the efficacy of the fixed combination to the individual components and to concomitant use of both components. Various factors inherent to study design such as medication run-in, washout periods and peak and trough effects have to be taken into consideration when analysing the demonstrated efficacy of fixed combinations. Fixed combination treatments offer effective IOP control while reducing the washout effect and exposure to preservatives. They are also convenient. However, fixed combinations also remove the possibility of titrating the individual components both in terms of concentration and timing of administration. In addition, fixed combinations might not always provide the same efficacy as proper use of the individual components. The clinician must make individualised assessments when weighing the convenience of these medications against their limitations for specific patients.     

药物临床试验机构备案要求及常见问题分析

2019-12-01药物临床试验机构开始实行备案管理。本文结合药物临床试验机构备案平台构建思路,着重介绍了备案平台的结构组成以及相关要求,梳理了药物临床试验机构备案过程中的常见问题,对机构如何满足备案要求进行分析和探讨,为药物临床试验机构更快更好地进行备案提供参考。     

Pharmacokinetics of antituberculosis drugs in patients

The pharmacokinetics of rifampin, isoniazid, and ethambutol were determined in 26 ambulatory male patients (aged 49.5 +/- 9.9 yr) with tuberculosis. Rifampin and isoniazid were given individually or together, with or without ethambutol; studies were done after a single dose and after chronic administration. Under the study conditions, with large variability in the extent of disease and physical status and history of alcohol and tobacco abuse and narrow age range, the pharmacokinetics of these three antituberculosis drugs were not modified significantly by patient age. Furthermore, appreciable drug-drug interactions did not occur when the three drugs were administered concurrently. Self-induction of rifampin clearance by chronic dosing with the drug may lead to subtherapeutic levels of rifampin. Administration of isoniazid and ethambutol in two divided doses resulted in peak plasma concentrations below the accepted therapeutic levels of the two drugs. Our findings indicate that at least in the middle-aged patients with tuberculosis, the current single daily dose, multiple-drug regimen is therapeutically sound pharmacokinetically, and clinicians do not have to make adjustments in dosages of these drugs for age and the extent of disease.     

抗结核药物靶点的研究进展

摘要：由结核分枝杆菌(Mycobacterium tuberculosis,Mtb)感染引起的结核病(TB)是世界上最致命的感染性疾病之一。因抗 结核药物的泛用与滥用,细菌耐药问题日渐凸显。近几十年仅有2种抗结核新药上市,由于药物使用中的副作用及其耐药菌株 的出现,急需开展针对Mtb新靶点的药物研究。本文围绕近几年全球最新报道的抗结核药物靶点及其相关化合物进行综述并加 以系统总结,以期在一定程度上为新型抗结核药物的研发提供参考。     

抗结核病药物包装、标签及说明书的调查分析

目的　促进防治结核病用药包装、标签及说明书的规范 ,保障抗结核药品质量 ,并为患者用药提供科学指导依据。方法　参照国家药品监督管理局令 (第 2 3号 )《药品包装、标签和说明书管理规定》并结合工作实践 ,对16个厂家、3种剂型、2 6个品种共 32个药品进行对照分析。结果　 32个药品中有 13个药品包装存在问题 ,占总数 4 1%,标签有 2 8个不符合规定 ,占总数百分率为 87.5 %,说明书项目均不完整。结论　重视包装环节、改进药品包装以保障药品质量 ;规范标签、说明书的内容 ,正确、全面指导患者用药。     

Oral antidiabetic drugs: effect of food on absorption of pioglitazone and metformin from a fixed-dose combination tablet

An open-label, randomized, crossover study involving 28 healthy subjects was conducted to compare the peak (Cmax) and total (AUC(lqc), AUC(infinity)) exposures to pioglitazone and metformin after single-dose administration of a fixed-dose combination tablet containing 15 mg of pioglitazone plus 850 mg metformin when given under fasted versus fed states, with a washout period of 7 days between treatments. Two different fixed-dose combination formulations (bilayer and pioglitazone-micronized fixed-dose combination tablets) were tested. The pioglitazone-micronized fixed-dose combination formulation was selected for clinical development and regulatory approval; the present study describes food effect results with this formulation. For pioglitazone, least squares mean ratios (fed/fasted) and the 90% confidence intervals of these ratios were 1.05 (0.93-1.18) for Cmax, 1.13 (1.02-1.25) for AUC(lqc), and 1.11 (1.01-1.22) for AUC(infinity). For metformin, these values were 0.72 (0.65-0.79) for Cmax, 0.87 (0.81-0.94) for AUC(lqc), and 0.87 (0.81-0.94) for AUC(infinity). Dosing with food resulted in median prolongation of tmax values by 1.5 hours for metformin and 2.0 hours for pioglitazone. Because bioequivalency criteria were met (fed/fasted 90% confidence interval between 0.80 and 1.25) for both pioglitazone and metformin AUC, fixed-dose combination tablets can be taken with or without food, but to minimize gastrointestinal adverse effects of metformin, the fixed-dose combination tablets are recommended to be taken with food.     

单克隆抗体类药物组织交叉反应常见问题的探讨

组织交叉反应是单克隆抗体类药物临床前安全性评价的重要组成部分。通过免疫组织化学方法考察单抗类药物与人体内非靶抗原的结合情况,为临床用药监测毒性提供参考。随着单克隆抗体研发由鼠源型向全人源化单抗的转变和发展,单抗药物的组织交叉反应试验也随之出现了一些问题,包括标本、组织选用、试验设计、抗体浓度选用和结果的综合分析等。本文结合笔者实际工作的经验和近年来国外组织交叉反应研究的情况,针对上述多方面问题进行了深入的探讨,以促进和推动我国单克隆抗体类药物的临床前安全性评价技术的发展。     

复方抗高血压药物注册临床研究应注意的问题

固定剂量的复方制剂既有临床合理联合用药的优势,同时又具有增加病人依从性,降低医疗费用等优势.针对不同上市基础的复方抗高血压药物,临床研究具有不同的内容,本文从国内已上市药品、国外上市,国内尚未上市药品、国内外均未上市复方抗高血压药品注册临床研究主要的考虑要点进行阐述.