喹诺酮类抗菌药物的药动学和药效学研究进展

喹诺酮类是目前临床普遍使用的一类抗菌药物.现从体外实验、动物实验和人体试验等方面对其药动学/药效学(PK/PD)研究进行了综述,并对PK/PD与细菌耐药及其在临床上的应用进行了简介.     

药动学-药效学结合模型的研究进展

本主要对近年来药动学．药效学结合模型在模型建立、药理学、毒理学、临床应用及新药研发等方面的进展进行了综述，并展望其发展前景。     

莫西沙星对社区获得性肺炎治疗作用的研究进展

社区获得性肺炎是指在医院外罹患的感染性肺实质炎症,是威胁人类健康的常见感染性疾病之一.莫西沙星作为第四代氟喹诺酮类药物,常用于社区获得性肺炎的治疗.其抗菌活性强,人体耐受性好,不良反应发生率低,具有广泛的临床应用前景.本文对莫西沙星的药动学、药效学和用药安全性问题进行综述,以为莫西沙星的合理应用提供参考.     

吲哚布芬治疗血栓性疾病研究进展

吲哚布芬是抗血小板聚集药物。该药物可逆性的抑制血小板环氧化酶，减少血栓烷素A2（TXA2）的生成，从而阻断血小板的聚集。临床研究已经评估了口服吲哚布芬预防与治疗下述疾病的疗效，包括：对房颤患者或非房颤患者血栓栓塞的二级预防；预防冠状动脉搭桥术后移植血管狭窄，间歇性跛行的治疗等。     

新一代抗菌药物Dalbavancin的研究进展

目的 综述新一代抗菌药物Dalbavancin的最新研究进展。 方法 通过检索Google Scholar以及Science Direct查阅大量近10年的相关文献,对Dalbavancin抗菌机制、抗菌活性、药动学、药效学以及安全性多角度综述分析。结果 Dalbavancin是一种糖肽类浓度依赖性抗菌药物,其体内外抗耐甲氧西林葡萄球菌(MIC50=0.06 mg·L^-1)的活性明显优于万古霉素(MIC50=1 mg·L^-1)、替考拉宁(MIC50=0.5 mg·L-1);其临床药动学表明具有每周给药1次的潜力,体内有效治疗浓度为20 mg·L^-1。结论 Dalbavancin是一种菌体耐药性突变率低,不良反应温和,药物毒性较小处于临床Ⅲ期研究的最具应用价值的新一代抗菌药物。     

氨氯地平与其他药物的相互作用研究进展

氨氯地平属于第三代钙离子拮抗剂（CCB）,主要用于心脑血管疾病的治疗。近期的研究发现,氨氯地平与多种药物存在相互作用,这些相互作用主要体现在药动学和药效学两个方面。药动学相互作用主要与肝药酶CYP450以及转运体P-gP（P-糖蛋白）有关。氨氯地平是CYP450和P-gp的底物,影响肝药酶或P-gp活性的药物,如抗病毒药物利托那韦、抗真菌药物伊曲康唑以及大环内酯内抗生素他克莫司等均可改变氨氯地平的药动学特征。药效学相互作用主要表现办疗效的改变,他汀类药物、血管紧张素转化酶抑制剂（ACEI）药物以及血管紧张素Ⅱ受体拮抗剂（ARB）等与氨氯地平具有协同作用,而氯吡格雷等其他药物与氨氯地平合用时,氨氯地平的疗效降低甚至失效。本文就近年来关于氨氯地平的相互作用研究做一综述。     

抗真菌药物的药动学和药效学研究进展

目的:介绍临床常用抗真菌药物的药动学和药效学研究进展,旨在为临床合理用药提供相关依据。方法:查阅国内、外相关文献,进行系统的阅读复习,并进行综合分析。结果:真菌感染发病复杂,诊断困难,预后较差,但是抗真菌药物研发的不断进步,为临床医生用药提供了更多选择,真菌感染的治疗和预后将逐步得到改善。结论:临床常用抗真菌药物的药动学和药效学研究,对于临床合理用药具有重要的指导意义。     

心血管系统药物的PK-PD模型研究进展

目的对心血管系统药物的药动学-药效学(PK-PD)模型研究进行回顾和展望。方法查阅文献资料,对相关内容进行总结。结果所得PK-PD模型以S-Emax模型居多。心血管系统药物的PK-PD模型日益呈现出精细化和复杂化的趋势。结论应用PK-PD模型对心血管系统药物的研究前景广阔,值得进一步推广。     

抗体药物偶联物药动学研究进展

抗体药物偶联物是临床上用于治疗多种恶性肿瘤的一种新型药物,其由单克隆抗体、细胞毒性小分子药物、抗体-药物连接子这3个部分构成。尽管抗体药物偶联物同时具有单克隆抗体的高靶向特异性和细胞毒性小分子药物的强细胞毒性,许多抗体药物偶联物在临床试验阶段仍因毒副作用大、有效性低等问题而被宣告失败。体内药动学分析和预测可为抗体药物偶联物的分子设计与给药方案确定提供重要参考。总结了影响抗体药物偶联物体内药动学的多方面因素以及体内药动学的常用生物分析手段,并为抗体药物偶联物的体内药动学和药效学的合理预测提供了理论参考。     

磷霉素的临床应用新进展

随着多重耐药菌(MDR)和全耐药菌(PDR)的出现和传播,临床分离菌对常见抗菌药物的耐药率呈增长趋势.在美国,仅磷霉素的口服制剂被批准用于治疗急性非复杂性尿路感染,而在一些国家,口服和静脉注射制剂可用于各种适应症.由于磷霉素具有独特的理化性质、作用机制及广泛的抗菌活性,故在重症感染、MDR/PDR感染方面的疗效引起了关...     

An overview of lefamulin for the treatment of community acquired bacterial pneumonia

ABSTRACT

Introduction

Lefamulin is a novel antibiotic that belongs to the pleuromutilin class with excellent activity against all microorganisms, including atypical pathogens, that cause community-acquired pneumonia (CAP).     

头孢美唑的药动药效学与临床

头孢美唑（ＣＭＺ）为一种半合成头霉素类抗生素，本品在日本和欧美已较广泛应用，国内从１９８８年起进行了临床观察及验证。结果表明ＣＭＺ有抗菌谱广，耐酶稳定，体内分布好，不良反应低等特点。具有良好的临床应用价值。本文概述了近年国内外有关ＣＭＺ的药动药效学及临床应用研究情况，以其供临床应用本品时参考。     

高效液相色谱法测定醋酸来法莫林的有关物质

摘要：目的 建立高效液相色谱法测定醋酸来法莫林的有关物质。方法 采用C18色谱柱(25 cm×4.6 mm,5 μm),流动相 A：60 mmol/L磷酸二氢钾溶液(磷酸调pH至2.5)-乙腈(80:20,V/V),流动相B：60 mmol/L磷酸二氢钾溶液(磷酸调pH至2.5)-乙腈 (50:50,V/V),梯度洗脱;流速1 mL/min;检测波长210 nm;柱温30℃;进样体积20 μL。结果 醋酸来法莫林与各有关物质分 离良好;醋酸来法莫林在0.50~75.33 μg/mL的浓度范围内,浓度与峰面积呈良好的线性关系,相关系数为1.000,醋酸来法莫林 的检测限为0.20 μg/mL。结论 该方法专属、可靠,可用于醋酸来法莫林有关物质的测定。     

冬凌草甲素研究进展

冬凌草甲素是从唇形科香茶菜属植物中提取出来的一种对映-贝壳杉烷型二萜类化合物,具有多种药理作用,尤其是抗肿瘤活性。本文对冬凌草甲素的衍生物、药效学及药代动力学等方面进行综述,并对冬凌草甲素的研究开发前景进行展望。     

新一代碳青霉烯类抗菌药比阿培南

比阿培南是碳青霉烯类抗菌药,对革兰阴性、革兰阳性菌和厌氧菌等均具有抗菌作用,并有良好的组织渗透性;药动学特性优良;用于治疗下呼吸道感染和泌尿道感染的临床有效率为89.5％ ～ 100％;本品药物不良反应轻微.大量的临床试验证明,比阿培南的临床应用疗效确切且安全.     

痰热清注射液治疗社区获得性肺炎的临床疗效观察

目的：观察痰热清注射液治疗社区获得性肺炎的疗效。方法：选取社区获得性肺炎患者173例,随机分为治疗组（95例）、对照组（78例）,对治疗前和治疗7d后患者总体疗效进行评估,并对两组肺部啰音消失天数和退热天数进行比较。结果：治疗组有效率显著高于对照组（P〈0.01）,治疗组肺部啰音消失天数和退热天数均短于（P〈0.05）和显著短于（P〈0.01）对照组。结论：痰热清注射液对社区获得性肺炎有较好疗效,对缓解患者肺部啰音,减少患者发热天数有一定作用。     

Antibiotic treatment for animals: effect on bacterial population and dosage regimen optimisation

Concern regarding antimicrobial resistance has led to proposals for the prudent use of antimicrobial agents. Whilst this is appropriate, it is not sufficient. This article proposes that dosage schedules should be developed to provide a basis for the rational use of antimicrobial drugs. This requires knowledge of resistance mechanisms and transfer, the biochemistry and structure of microorganisms and both the pharmacodynamics and pharmacokinetics of antimicrobial drugs. Dosage schedules should maintain concentrations at the site of infection in excess of MIC₉₀ for bacteriostatic drugs and bactericidal drugs acting primarily by time-dependent mechanisms whilst they should provide high AUIC and C_max/minimum inhibitory concentration (MIC) values for agents acting mainly by concentration-dependent mechanisms. It is proposed that pharmacodynamic and population pharmacokinetic data should be integrated through use of the sigmoidal E_max equation, together with mathematical modelling and appropriate statistical analyses, to take account of the natural variation in drug pharmacodynamics and pharmacokinetics.     

Ceftobiprole medocaril for the treatment of community-acquired pneumonia

Introduction: Ceftobiprole is a novel broad-spectrum cephalosporin with excellent activity against a broad range of pathogens that are important in community-acquired pneumonia (CAP), including drug-resistant pneumococci, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa.

Areas covered: This article reviews the spectrum of activity, the main pharmacological and pharmacodynamic characteristics of ceftobiprole as well its clinical efficacy and safety in the treatment of CAP in adult patients.

Expert opinion: Taking into account that the current treatment guidelines for CAP recommend the use of an adequate empirical therapy to improve its prognosis, ceftobiprole shows a profile of antimicrobial activity that would cover most etiological agents in patients with risk factors for infection caused by multidrug resistant organisms. The results of the pivotal clinical trial of patients hospitalized with CAP treated with ceftobiprole showed a high rate of clinical cure. The clinical tolerance of ceftobiprole in clinical trials was generally very good. These findings make ceftobiprole a good parenteral therapeutic alternative for the empirical treatment of CAP that requires hospitalization, especially in patients with risk factors for CAP caused by resistant microorganisms.     

Ceftaroline fosamil in the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections

Ceftaroline fosamil is a cephalosporin antibacterial approved by the US Food and Drug Administration (FDA) for use in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). After intravenous administration, ceftaroline fosamil is rapidly converted to its bioactive metabolite, ceftaroline. Ceftaroline has broad-spectrum in vitro activity against Gram-positive and Gram-negative bacteria, including contemporary resistant Gram-positive phenotypes, such as methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae. Because of its unique spectrum of activity, the Clinical and Laboratory Standards Institute (CLSI) designated ceftaroline as a member of a new subclass of β-lactam antimicrobials, cephalosporins with anti-MRSA activity. The activity of ceftaroline against S. aureus extends to heteroresistant vancomycin-intermediate, vancomycin-intermediate, vancomycin-resistant and daptomycin-nonsusceptible isolates. Ceftaroline has low minimum inhibitory concentrations (MICs) for all tested species of streptococci, and has potent activity against S. pneumoniae isolates with varying degrees of penicillin resistance. The activity of ceftaroline is limited against Enterococcus faecalis and Enterococcus faecium and against anaerobes such as Bacteroides fragilis. The in vitro activity of ceftaroline includes many Gram-negative pathogens, but does not extend to bacteria that produce extended-spectrum β-lactamases, class B metallo-β-lactamases or AmpC cephalosporinases, or to most nonfermentative Gram-negative bacilli. Ceftaroline fosamil has been studied for the treatment of complicated skin and skin structure infections (cSSSI) and community-acquired pneumonia (CAP) in phase III randomized, double-blind, international, multicentre noninferiority clinical trials. Two identical trials (CANVAS 1 and CANVAS 2) compared the efficacy of ceftaroline fosamil with that of vancomycin plus aztreonam in 1378 adults with cSSSI. Results demonstrated that ceftaroline was noninferior to vancomycin plus aztreonam, with 91.6% in the ceftaroline fosamil group (pooled analysis) achieving clinical response compared with 92.7% in the vancomycin plus aztreonam group (difference -1.1%, 95% CI -4.2, 2.0). An additional analysis evaluated clinical cure in a subgroup of patients who met the FDA guidance definition of ABSSSI at treatment day 3. Clinical response, defined as cessation of lesion spread and absence of fever, was 74.0% in the ceftaroline fosamil group compared with 66.2% in the vancomycin plus aztreonam group (treatment difference 7.8%, 95% CI 1.3, 14.0). Clinical efficacy of ceftaroline fosamil in 1240 hospitalized adults with CAP was compared with that of ceftriaxone in two additional phase III trials (FOCUS 1 and FOCUS 2). Of note, because ceftriaxone does not have activity against MRSA, patients with confirmed or suspected MRSA CAP were excluded from the FOCUS trials. Results demonstrated that ceftaroline was noninferior to ceftriaxone, with 84.3% in the ceftaroline fosamil group achieving clinical cure compared with 77.7% in the ceftriaxone group (difference 6.7%, 95% CI 1.6, 11.8). An additional analysis of the trials was conducted in patients with moderate to severe CAP and at least one proven typical bacterial pathogen at baseline (i.e. CABP). Day 4 clinical response rates were 69.5% for ceftaroline and 59.4% for ceftriaxone (difference 10.1%, 95% CI -0.6, 20.6). In the phase III trials, adverse event rates were similar between groups. Overall, ceftaroline is well tolerated, which is consistent with the good safety and tolerability profile of the cephalosporin class. In summary, ceftaroline fosamil is a broad-spectrum parenteral cephalosporin with excellent in vitro activity against resistant Gram-positive pathogens, including MRSA, as well as many common Gram-negative organisms. It is a welcome treatment option for ABSSSI and CABP.     

莫西沙星药理特性与用药安全性研究进展及分析

目的分析莫西沙星药理特性,关注用药不良反应,提出应对措施。方法检索相关的国内外文献,从药动学、药效学、作用机制、耐药性、抗菌谱等方面进行分析,并通过对不良反应病例的探讨,提出应对措施。结果莫西沙星具有良好的药动学、药效学特性,抗菌谱广、耐药性低、药物相互作用少,针对其不良反应,按照过敏史、年龄、基础疾病等对使用者进行严格选择。结论莫西沙星对细菌的结合能力和细胞膜的穿透能力强,抗菌后效应强大而持久,在临床各科都有广泛的应用。临床医师需根据患者不同情况制定个体化用药方案。