新的广谱、高效喹诺酮类抗菌药gemifloxacin

gemifloxacin是由韩国LG公司研制 ,美国史克公司开发的新的广谱高效喹诺酮类抗菌药 ,它对肺炎链球菌的MIC90 为 0 0 3mg/L ,其活性是曲伐沙星和莫西沙星的 4～ 8倍 ,是环丙沙星的 3 0～ 60倍 ;对葡萄球菌 (金黄色葡萄球菌除外 )的MIC90 为 0 0 3～ 2mg/L ,其活性是曲伐沙星和莫西沙星的 2～ 4倍 ,是环丙沙星的 8～ 3 2倍。临床研究表明 ,它对下呼吸道感染具有很好的临床疗效 ,与阿莫西林 /克拉维酸合剂的疗效相当 ,而优于曲伐沙星 ;对尿道感染也有很好的治疗效果 ,临床治愈率为 98 7%。由于gemifloxacin疗效确切 ,而不良反应轻微 。

gemifloxacin的药理和临床研究进展

gemifloxacin是新的第四代喹诺酮类抗菌药 ,其抗菌谱广 ,对革兰氏阳性菌有很强的杀菌活性 ,同时也保持了对革兰氏阴性菌的抗菌活性 ,而且对厌氧菌、枝原体、衣原体也有一定的抗菌作用。gemifloxacin由于 C7-位被氨基吡咯环取代 ,与细菌 DNA促旋酶和拓扑异构酶 的亲和力明显增强 ,因此能有效地抑制细菌 DNA复制并发挥杀菌效能。gemifloxacin对金黄色葡萄球菌、肺炎链球菌有极强的活性 ,MIC90 分别为 0 .0 6 3～ 1和 0 .0 15 mg/L;对喹诺酮耐药性肺炎链球菌也有很强的活性 ,MIC为 0 .0 0 4～ 0 .5 mg/ L。对大多数革兰氏阴性菌的抗菌活性均小于 0 .5 mg/ L,与环丙沙星相当 ;但对铜绿假单胞菌的活性较环丙沙星稍弱。对流感嗜血菌、粘膜炎莫拉氏菌、军团菌等也有较强的活性 ;对革兰氏阳性厌氧菌有很好的活性 ,对革兰氏阴性厌氧菌的活性有限。 gemifloxacin口服吸收迅速 ,血药浓度的平均达峰时间为 1h;组织分布广 ,平均分布容积达 4 .2± 0 .8L/ kg,平均消除半衰期为 7.4± 2 .0h,和其他药物的相互作用少 ,轻 -中度肝肾功能不全的患者均能良好耐受。gemifloxacin临床疗效确切 ,32 0 mg/ d可有效治疗敏感菌所致的呼吸道、泌尿道和其他系统的感染 ;不良反应轻微 ,常见的不良反应主要表现为轻度头晕、恶心、皮?

Anodic voltammetric determination of gemifloxacin using screen-printed carbon electrode

The electrochemical oxidation behavior and voltammetric assay of gemifloxacin were investigated using differential-pulse and cyclic voltammetry on a screen-printed carbon electrode.The effects of pH,scan rates,and concentration of the drug on the anodic peak current were studied.Voltammograms of gemifloxacin in Tris-HCl buffer（pH 7.0） exhibited a well-defined single oxidation peak.A differential-pulse voltammetric procedure for the quantitation of gemifloxacin has been developed and suitably validated with respect to linearity,limits of detection and quantification,accuracy,precision,specificity,and robustness.The calibration was linear from 0.5 to 10.0 μM,and the limits of detection and quantification were 0.15 and 5.0 μM.Recoveries ranging from 96.26% to 103.64% were obtained.The method was successfully applied to the determination of gemifloxacin in pharmaceutical tablets without any pre-treatment.Excipients present in the tablets did not interfere in the assay.

Development and Validation of Stability Indicating HPTLC Assay for Determination of Gemifloxacin Mesylate in Dosage Forms

Simple and sensitive stability-indicating high performance thin layer chromatography (HPTLC) assay was developed and validated for quantitative determination of the antibacterial drug, gemifloxacin mesylate (GFX) in presence of its degradation products and ambroxol hydrochloride. The chromatographic separation was performed on HPTLC precoated silica gel plate 60F254 as stationary phase. The mobile phase consisted of a mixture of ethyl acetate: methanol: 25% ammonia, (8:4.5:3, v/v/v). The detection was performed using fluorescence mode and the emission intensity was measured using optical filter K400 after excitation at 342 nm. The Rf value for GFX was 0.47 ± 0.03. Good correlation coefficient was obtained over the concentration range of 1.5 - 180 ng/band. The LOD and LOQ of the proposed method were 0.28 and 0.86 ng/band, respectively. The proposed method was successfully applied for the analysis of GFX in its single and combined dosage forms. Moreover, it was utilized to investigate the kinetics of acidic, alkaline, neutral, oxidative and photolytic degradation of the drug. The apparent kinetic-order rate constants and half-life times of the degradation process were calculated. Furthermore, the proposed method was successfully applied for investigating the factors affecting the storage of GFX.

Partitioning Behavior of Gemifloxacin in Anionic, Cationic and Nonanionic Surfactants. Calculation of Dermal Permeability Coefficient

Transdermal delivery acts as an alternative to oral delivery of drugs and possibly provids also an alternative to hypodermic injection. Transdermal delivery when compared to oral route has a variety of advantages namely: avoiding the degradation of drugs in the stomach environment, providing steady plasma levels, avoiding first-pass metabolism, increaseing patient compliance, easy to use, non-invasive and inexpensive, increasing the therapeutic index with a simultaneous decrease in drug side effects. Despite these advantages, one of the greatest challenges to transdermal delivery is that only a limited number of drugs are amenable to administration by this route. Gemifloxacin, a broad spectrum fourth generation quinolone antibacterial agent has pharmacokinetic characteristics (particularly its low maximum plasma concentration, obtained following repeat oral dose of 320 mg) that makes it a potential target for transdermal delivery. The objective of the study was to explore the possibility of surfactants (anionic, cationic and nonionic) acting as dermal enhancers of gemifloxacin assuming that the drug is to be formulated into topical or transdermal pharmaceutical dosage form. To accomplish the objective, gemifloxacin was partitioned between chloroform and surfactants containing varying concentrations of sodium lauryl sulfate, cetyltrimethylammonium bromide, polysorbate-20 and polysorbate-80. The data obtained were used to estimate the dermal permeability coefficient. The partitioning was carried out by shake flask method at room temperature. It was observed that all the surfactants decreased the partition behavior of gemifloxacin when compared to that of water alone. Sodium lauryl sulfate produced the most decreasing partition effect at the highest concentration studied (2% w/v). The permeability coefficient (Kp) was estimated from the partition coefficient data and the molecular weight of the drug. As permeability coefficient is an important descriptor for evaluating dermal absorption of drugs employed in clinical treatment of various dermal accessible ailments, the results of the study suggest that the investigated surfactants might not be potential transdermal enhancers of gemifloxacin.

Gemifloxacin for the treatment of community-acquired pneumonia and acute exacerbation of chronic bronchitis： a meta-analysis of randomized controlled trials

Background Gemifloxacin is a fluoroquinolone antibiotic with broad spectrum of antibacterial activity.The aim of the study was to evaluate the comparative effectiveness and safety of gemifloxacin for the treatment of patients with community-acquired pneumonia （CAP） or acute exacerbation of chronic bronchitis （AECB）.Methods We performed a meta-analysis of randomized controlled trials （RCTs） comparing gemifloxacin with other approved antibiotics.The PubMed,EMBASE,Chinese Biomedical Literature Database and the Cochrane Central Register of Controlled Trials were searched,with no language restrictions.Results Ten RCTs,comparing gemifloxacin with other quinolones （in 5 RCTs） and β-lactams and/or macrolides （in 5 RCTs）,involving 3940 patients,were included in this meta-analysis.Overall,the treatment success was higher for gemifloxacin when compared with other antibiotics （odds ratio 1.39,95% confidence interval 1.15-1.68 in intention-to-treat patients,and 1.33,1.02-1.73 in clinically evaluable patients）.There was no significant difference between the compared antibiotics regarding microbiological success （1.19,0.84-1.68） or all-cause mortality （0.82,0.41-1.63）.The total drug related adverse events were similar for gemifloxacin when compared with other quinolones （0.89,0.56-1.41）,while lower when compared with β-lactams and/or macrolides （0.71,0.57-0.89）.In subgroup analyses,administration of gemifloxacin was associated with fewer cases of diarrhoea and more rashes compared with other antibiotics （0.66,0.48-0.91,and 2.36,1.18-4.74,respectively）.Conclusions The available evidence suggests that gemifloxacin 320 mg oral daily is equivalent or superior to other approved antibiotics in effectiveness and safety for CAP and AECB.The development of rash represents potential limitation of gemifloxacin.

Spectrophotometric methods for the determination of gemifloxacin in pharmaceutical formulations

This paper describes two simple spectrophotometric methods for the determination of the antibiotic gemifloxacin mesylate(GFX)in pharmaceutical formulations.The first(A)is an indirect method in which oxidation of the drug with a known excess of cerium(IV)sulphate is followed by determination of the residual oxidant by adding excess methyl orange and measuring residual dye at 507 nm.The second(B)is a derivatisation method involving reaction of GFX with 1,2-naphthoquinone-4-sulphonate(NQS)in alkaline medium(pH 11)to form an orange-coloured product exhibiting maximum absorption(lmax)at 411 nm.The methods were linear in the concentration ranges 2–9 and 5–30 mg/mL for methods A and B,respectively,with intra-day precision(as RSD)o1.5%for both.When applied to the determination of GFX in pharmaceutical tablets,the results were in good agreement with those obtained by capillary electrophoresis.The two methods are useful for routine analysis of GFX in quality control laboratories.

链阳菌素(streptogramins)的研究进展

细菌耐药性是全球共同关注的问题 ,链阳菌素是一种结构独特的新型抗生素 ,本文介绍了它的抗菌活性、作用机制、药代动力学特点以及国外临床应用等。

氟喹诺酮药物研究新进展

氟喹诺酮药物是近 2 0年来抗菌药的研究热点之一 ,本文分 3部分综述自 1997年以来该类药物研究新进展 :①最近上市的新品种 ,包括莫西沙星和加替沙星 ;②即将上市的药物 (吉米沙星 ) ;③氟喹诺酮药物的安全性以及由于毒性而从市场撤消或限制使用的品种 ,包括曲伐沙星、替马沙星。

新一代广谱氟喹诺酮类抗菌药吉米沙星

综述吉米沙星的抗菌作用、药动学及临床评价。吉米沙星是一种新型的广谱氟喹诺酮类抗菌药,抗菌谱广,抗菌作用强,不良反应少,耐受良好。体外能显著抑制肺炎链球菌,对其他一些菌如葡萄球菌、单核细胞增生性李斯特菌、流感嗜血杆菌和卡他莫拉菌也显出明显的抗菌作用。

单剂口服吉米沙星临床药动学研究

目的研究单剂口服吉米沙星在中国健康志愿者中的药动学特性,为制订用于中国人的安全有效的给药方案提供依据。方法12名受试者随机、开放、3交叉单剂空腹口服吉米沙星片剂160mg、320mg和480mg。以高效液相色谱(HPLC)-荧光法测定血、尿样中吉米沙星药物浓度。应用Winnonlin分析软件计算药动学参数。结果受试者单剂空腹口服吉米沙星160mg、320mg和480mg后体内过程均符合非房室模型,平均血清Cmax分别为(0.70±0.19)mg/L、(1.40±0.32)mg/L和(1.84±0.35)mg/L;Tmax中位数分别为1(0.5,2)h、1(0.5,2)h和1.25(1,2)h;平均t1/2分别为(7.06±1.22)h、(7.02±0.94)h和(7.28±0.81)h;平均AUC0-24h分别为(3.86±0.56)mg.h/L、(7.61±0.93)mg.h/L和(11.47±1.68)mg.h/L;平均AUC0-∞分别为(4.01±0.57)mg.h/L、(7.71±0.92)mg.h/L和(11.62±1.72)mg.h/L;平均Vd分别为(411.45±77.88)L、(423.47±59.48)L和(439.21±55.55)L;平均CLt分别为(40.71±6.22)L/h、(42.10±5.46)L/h和(42.26±7.14)L/h;给药后48h内平均累积尿排出率分别为(38.95±6.14)%、(37.84±6.62)%和(35.57±5.07)%。结论中国健康受试者单次空腹口服吉米沙星160～480mg结果显示其符合线性药动学的特性,消除半衰期长。给药量的约40%以原形药物经肾排出。

壳聚糖包覆的CdTe量子点荧光猝灭法测定吉米沙星

以壳聚糖包覆的CdTe量子点为荧光探针,基于荧光猝灭法建立了吉米沙星定量测定方法。结果表明,体系的荧光强度与吉米沙星浓度在3.46×10-9～3.46×10-7 g.L-1范围内呈良好的线性关系(r=0.999 2),线性回归方程为F0/F=1.063 7+0.016 7c(g.L-1)。对2.77×10-7 g.L-1吉米沙星溶液进行7次平行测定的相对标准偏差为2.7%,基于荧光猝灭法相关理论证明了该相互作用过程为静态猝灭。本方法灵敏度高,检测线性范围宽,为吉米沙星定量测定提供了简便可靠的方法。

新一代广谱氟喹诺酮类抗菌药物吉米沙星

吉米沙星是韩国LG Life Science公司研制的第四代氟喹诺酮类抗菌新药,它同时作用于细菌DNA旋转酶和DNA拓扑异构酶IV,提高了抗菌活性,降低耐药率。吉米沙星除了保持对革兰阴性菌的强大抗菌活性外,对包括多重耐药性肺炎链球菌在内的革兰阳性菌也具有良好的活性。吉米沙星具有良好的药动学性质,组织渗透性强,能强力杀灭感染部位致病菌。它的药物间相互作用少,有较好的安全性和耐受性,是临床上治疗慢性支气管炎急性发作、社区获得性肺炎和急性鼻窦炎的良好药物。

吉米沙星与左氧氟沙星治疗下呼吸道感染的随机对照比较

目的:评价吉米沙星治疗下呼吸道感染的有效性和安全性。方法:采用随机对照单盲试验。33例下呼吸道感染病人,其中社区获得性肺炎(CAP)14例,慢性支气管炎急性发作(AECB)19例,随机分为2组,试验组17例,对照组16例。试验组予吉米沙星320 mg,每日1次,CAP病人疗程7～14 d,AECB病人疗程5 d。对照组予左氧氟沙星200 mg,每日2次,CAP病人疗程7～14 d,AECB病人疗程7 d。结果:治疗结束后d 1,临床有效率试验组为71%,对照组为93%;治疗结束后d 7,临床有效率2组均为100%。2组疗效比较无显著差异(P>0.05),不良反应发生率亦无显著差异(P>0.05)。结论:吉米沙星与左旋氧氟沙星治疗下呼吸道感染的临床疗效相似。

不同地区4家医院临床分离菌株对吉米沙星、左氧氟沙星和莫西沙星的耐药性分析

目的:了解国内不同地区4家医院临床分离菌株对吉米沙星、左氧氟沙星和莫西沙星的耐药性,为临床合理使用氟喹诺酮类抗菌药物提供参考。方法:收集2015年四川省人民医院、复旦大学附属华山医院、广州医科大学附属第一医院和甘肃省人民医院临床分离菌株,参照2016年美国临床和实验室标准协会相关要求,采用E试验测定细菌对抗菌药物的敏感性。采用纸片法筛选和酶抑制剂增强确证试验检测大肠埃希菌、肺炎克雷伯菌、产酸克雷伯菌和奇异变形杆菌中产超广谱β-内酰胺酶(extended spectrum β-lactamase,ESBL)菌株。结果:共收集到临床分离菌株539株,其中大肠埃希杆菌120株,肺炎克雷伯菌117株,肺炎链球菌108株,流感嗜血杆菌111株,卡他莫拉菌83株。大肠埃希菌对吉米沙星、左氧氟沙星的耐药率分别为56.7%、48.3%,其中产ESBL菌株对吉米沙星、左氧氟沙星的耐药率分别为66.7%、62.2%,非产ESBL菌株对吉米沙星、左氧氟沙星的耐药率分别为41.5%、34.0%。肺炎克雷伯对吉米沙星、左氧氟沙星的耐药率分别为36.8%、19.7%,其中产ESBL菌株对吉米沙星、左氧氟沙星的耐药率分别为81.6%、39.5%,非产ESBL菌株对吉米沙星、左氧氟沙星的耐药率分别为14.7%、12.1%。肺炎链球菌对吉米沙星、左氧氟沙星和莫西沙星的耐药率分别为2.8%、4.6%和2.8%;吉米沙星、左氧氟沙星和莫西沙星对流感嗜血杆菌的MIC_(90)范围为0.5～0.75μg/ml,左氧氟沙星、莫西沙星对流感嗜血杆菌的敏感率分别为100%、93.7%;吉米沙星对卡他莫拉菌的MIC_(50)、MIC_(90)分别为0.016、0.125μg/ml。结论:大肠埃希菌和肺炎克类伯菌对氟喹诺酮类抗菌药物的耐药率较高,但肺炎链球菌、流感嗜血杆菌和卡他莫拉菌对上述3种氟喹诺酮类抗菌药物高度敏感。

喹诺酮类药物母环的衍变及合成研究

介绍了近年来喹诺酮类药物的分类,总结了喹诺酮类药物母环的分类及其衍变,重点介绍了最新热门药物吉米沙星母环的常见的化学合成方法。

2,6-二氯-5-氟烟酰乙酸乙酯的合成

2,6-二氯-5-氟烟酰乙酸乙酯（1）是氟喹诺酮类抗菌药吉米沙星（gemifloxacin）的重要中间体。文献以2,6-二氯-5-氟烟酸为原料,依次与氯化亚砜和丙二酸酯反应后,再经水解、脱羧制得1,此法对环境污染的较严重。

甲磺酸吉米沙星对泌尿道常见致病菌的PK-PD研究

目的：开展吉米沙星对泌尿道常见致病菌的药动学／药效学研究。方法：测定吉米沙星对临床分离的泌尿道常见致病茵的最小抑菌浓度及最低杀菌浓度；测定健康受试者口服甲磺酸吉米沙星片320mg后尿药浓度并计算Cmax／MIC90和AUC24h／MIC90。结果：吉米沙星对临床分离的泌尿道常见致病茵的敏感率较低。健康受试者口服甲磺酸吉米沙星片320mg后尿药峰浓度C。。。为（144±124）ug／mL，尿药浓度时间曲线下面积AUC24h为（1368±671）肚g·mL-1·h。尿液中吉米沙星对大肠埃希茵、铜绿假单胞菌、粪肠球菌的Cmax／MIC90为2．9～5．8、AUC：4h／MIC90〉30；对肺炎克雷伯菌、屎肠球菌AUC24h／MIC90为19．25。结论：吉米沙星可有效清除泌尿道感染的大肠埃希菌、铜绿假单胞茵、粪肠球菌，并避免耐药茵产生；对肺炎克雷伯茵、屎肠球菌生长有抑制作用。

氟喹诺酮类药物的进展与临床应用评价

目的 :介绍第 4代氟喹诺酮类药物的抗菌作用特点和临床应用的进展历程。方法 :采用中、外文献综述方法。结果 :新 1代氟氟喹诺酮类药物的抗菌谱更趋广泛 ,对需氧菌和厌氧菌的抗菌能力较前 3代的同类药物均有所增强。结论 :第 4代氟喹诺酮类药物的抗菌谱广、杀菌力强、吸收快、体内分布广、血浆半衰期较长 ,有望在临床上广泛用于各种感染 。