左氧氟沙星根治幽门螺杆菌的临床研究

<正>幽门螺杆菌(helicobacter pylori,HP)感染治疗的研究一直是上消化道疾病治疗中的热点,目前已确认慢性胃炎、消化性溃疡、胃癌和胃黏膜相关淋巴组织(MALT)淋巴瘤等4种疾病与幽门螺杆菌感染     

含左氧氟沙星的三联方案对Hp阳性消化性溃疡的疗效观察

目的探讨以左氧氟沙星为主的三联疗法对根除幽门螺杆菌疗效及安全性。方法收集本院自2006年1月至2008年11月经胃镜检查和Hp检测阳性的消化性溃疡患者,随机分为两组,A组奥美拉唑20mg+阿莫西林1g+克拉霉素0.5mg,2次/d,连续10d,B组奥美拉唑20mg+阿莫西林1g,2次/d+左氧氟沙星0.4mg1次/d,连续10d。然后再继续单独给予各组奥美拉唑20mg,2次/d,连续3周,于用药结束后第28天复查胃镜及检测Hp,观察溃疡愈合情况及Hp根除情况,并于用药过程中及用药后患者症状改善情况及出现的不良反应进行随访、统计、评估。结果A组患者根除率为68.3%,B组患者根除率为89.7%。溃疡愈合率A组为89.2%,B组为90.2%,不良反应发生率A组为18.5%,B组为14.2%。结论含左氧氟沙星的四联方案治疗幽门螺杆菌根除率高,安全性好。     

左氧氟沙星三联疗法根治幽门螺杆菌感染

目的探讨含左氧氟沙星的三联疗法治疗幽门螺杆菌感染的有效性和安全性。方法选择62例确诊为幽门螺杆菌感染的患者,按照随机原则均分为观察组与对照组,其中观察组患者采用雷贝拉唑、阿莫西林、左氧氟沙星,对照组患者采用雷贝拉唑、阿莫西林、克拉霉素,所有患者均治疗两周后复查胃镜和快速尿素酶试验,比较两组治疗后幽门螺杆菌的根除率以及不良反应的发生率。结果观察组患者的幽门螺杆菌根除率为90.32%,对照组患者幽门螺杆菌根除率为70.97%,前者明显优于后者(P<0.05),两组患者的不良反应发生率无统计学差异(P>0.05)。结论采用左氧氟沙星联合阿莫西林和雷贝拉唑治疗幽门螺杆菌感染根除率高,用药简单方便,不良反应较少,易于患者接受,值得临床推广。     

左氧氟沙星在治疗幽门螺杆菌中的疗效观察

目的观察左氧氟沙星治疗幽门螺杆菌(Hp)感染的疗效。方法将2011年6月至2012年6月就诊的166例Hp阳性胃、十二指肠溃疡患者,随机均分为A组和B组各83例,A组给予质子泵抑制剂标准剂量,左氧氟沙星0.2g,阿莫西林1.0g,枸橼酸铋钾0.22g;B组给予标准剂量质子泵抑制剂,阿莫西林1.0g,甲硝唑0.2g,枸橼酸铋钾0.22g;两组均口服每日2次,疗程7d,观察两组Hp根除率的差异,记录不良反应。结果 A组Hp根除率为88.84%;溃疡愈合率为93.93%。B组Hp根除率为56.67%,溃疡愈合率为93.75%。两组比较,溃疡愈合率差异无统计学意义(P>0.05),但Hp根除率A组较B组高(P<0.05)。两组的不良反应发生率分别为8.33%与9.52%,差异无统计学意义(P>0.05)。结论左氧氟沙星治疗Hp感染效果好,症状缓解快,不良反应小,值得在临床上推广应用。     

泮托拉唑、左氧氟沙星、阿莫西林三联疗法根除幽门螺杆菌疗效观察

目的观察泮托拉唑、左氧氟沙星、阿莫西林三联疗法根除幽门螺杆菌(HP)的疗效及安全性。方法将90例患者随机分为治疗组45例,用泮托拉唑(40mg,2次/d),左氧氟沙星(0.2g,2次/d),阿莫西林(1.0g,2次/d),治疗7d,溃疡患者继续用泮托拉唑40mg,每日1次,共3周。对照组45例,用奥美拉唑(20mg,2次/d),阿莫西林(1.0g,2次/d),替硝唑(0.5g,2次/d),治疗7d,溃疡患者继续用奥美拉唑20mg,每日1次,共3周。治疗结束后4周复查。结果治疗组HP根除率93.3%,对照组HP根除率77.8%(P<0.05)。治疗组溃疡愈合率、不良反应发生率分别为95.7%,4.4%,对照组溃疡愈合率、不良反应发生率分别为91.3%,6.7%(P>0.05)。结论治疗组三联疗法根除HP是有效的方案。     

左氧氟沙星对幽门螺杆菌体外抗菌活性的评价

目的 体外试验检测左氧氟沙星对幽门螺杆菌(Helicobacter.pylori)的敏感性，并以克拉霉索和阿莫西林进行对照研究。方法 琼脂稀释法检测左氧氟沙星对52株幽门螺杆菌的最低抑菌浓度，同时比较在MH培养基pH为4．0、5．0、7．0条件下的MIC。结果 左氧氟沙星耐药菌株1．9％，阿莫西林耐药菌株11．5％，克拉霉索耐药菌株25％。同时对阿莫西林和克拉霉索耐药的菌株(9．6％)，对左氧氟沙星均敏感。左氧氟沙星耐药率明显低于克拉霉素(P＜0．01)，阿莫西林的耐药率也低于克拉霉素(P＜0．05)，但与左氧氟沙星的耐药率无明显差异(P＞0．05)。左氧氟沙星在酸性环境下抗菌活性降低。结论 本地区幽门螺杆菌耐药菌株多见，左氧氟沙星是一种可供选择的治疗药物。     

左氧氟沙星根除幽门螺杆菌的初步尝试

目的:探讨奥美拉唑加左氧氟沙星、呋喃唑酮三联7d疗法根除幽门螺杆菌的疗效及安全性。方法:选择64例HP阳性的慢性胃炎和消化性溃疡患者作为治疗组,采用奥美拉唑20mg、左氧氟沙星200mg、呋喃唑酮100mg,bid,疗程7d,同期门诊使用丽珠胃三联的70例病人作为对照组,疗程7d。疗程结束后1mon以上复查C尿素呼气试14验,观察HP根除率及不良反应。结果:治疗组和对照组的HP根除率和不良反应发生率分别为90.6%、84.3%和7.8%、12.9%,治疗组和对照组每例根除HP费用分别为100.00元和227.50元。结论:奥美拉唑加左氧氟沙星、呋喃唑酮三联7d疗法是根除HP的理想方案,且费用低,副作用小,值得推广。     

左氧氟沙星三联方案补救根治幽门螺杆菌疗效

目的：研究左氧氟沙星三联方案补救根治幽门螺杆菌（Hp）的疗效和药物不良反应。方法：经传统三联根除脚治疗失败患者116例,随机分为A、B两组,A组60例,给予以左氧氟沙星为基础的三联补救治疗10d;B组56例给予常规四联补救治疗10d,观察两组疗效及不良反应。结果：A组54例完成治疗及随访,其中50例补救治疗成功,7例发生药物不良反应;B组51例完成治疗及随访,其中39例补救治疗成功,7例发生药物不良反应。A组的脚根除率明显高于B组（P〈0．05）。结论：以左氧氟沙星为主的三联方案补救根治印的疗效优于常规四联补救治疗,疗程短、不良反应少,值得临床推广。     

含左氧氟沙星三联疗法根除幽门螺杆菌感染临床疗效观察

目的 观察含左氧氟沙星短程三联疗法根除幽门螺杆菌(Hp)感染的疗效及安全性.方法 选择124例符合条件的Hp阳性伴糜烂性胃炎或消化性溃疡患者随机分为两组.治疗组采取标准剂量的奥美拉唑(20mg,2次/日)加左氧氟沙星(200 mg,2次/日)加呋喃唑酮(100 mg,2次/日),治疗7日.对照组采取标准剂量的奥美拉唑(20 mg,2次/日)加阿莫西林(1 000 mg,2次/日)加呋喃唑酮(100 mg,2次/日),治疗7日.溃疡患者继用奥美拉唑(20 mg,2次/日),共3周.疗程结束4周后复查Hp,观察Hp根除率及不良反应.结果 治疗组和对照组的Hp根除率、不良反应发生率分别为88.06%、7.46%和84.21%、14.04%.两组根除率差异无统计学意义(P>0.05),治疗组不良反应发生率低于对照组(P<0.05).结论 左氧氟沙星根除Hp疗效亦较好,不良反应发生率低,可作为一线用药之一.     

泮托拉唑、左氧氟沙星、阿莫西林三联疗法根除幽门螺杆菌相关性消化性溃疡疗效观察

目的 比较应用左氧氟沙星联合泮托拉唑和阿莫西林(观察组)与应用甲硝唑联合泮托拉唑和阿莫西林(对照组)治疗消化性溃疡及根除幽门螺杆菌感染的疗效.方法 经胃镜检查证实为消化性溃疡及尿素酶试验检测HP证实为阳性的54例患者,随机分为观察组及对照组各27例,疗程7 d.经一疗程治疗后,比较两组疗效.结果 HP根除,观察组为88.9%,对照组为70.4%,差异有统计学意义(P＜0.05);溃疡愈合总有效率,观察组为96.3%,对照组为92.6%,差异无统计学意义(P＞0.05).结论 HP耐药菌株日益增多,左氧氟沙星联合泮托拉唑和阿莫西林三联疗法是一种安全、疗效高,耐受性好的根除HP感染,促进溃疡愈合的理想方法之一.     

Transport characteristics of grepafloxacin and levofloxacin in the human intestinal cell line Caco-2.

Transport characteristics of grepafloxacin and levofloxacin across the apical membrane of Caco-2 cells were examined. Both grepafloxacin and levofloxacin uptakes increased rapidly, and were temperature-dependent. Grepafloxacin and levofloxacin uptakes showed concentration-dependent saturation with Michaelis constants of 3.9 and 9.3 mM, respectively. Uptake of grepafloxacin and levofloxacin increased in Cl(-)-free and ATP depleted conditions, suggesting the involvement of an efflux transport system different from the uptake mechanism. However, cyclosporin A, a typical inhibitor of P-glycoprotein, did not affect the uptake of these drugs. Unlabeled grepafloxacin, unlabeled levofloxacin and quinidine inhibited the uptake of grepafloxacin and levofloxacin under Cl(-)-free conditions. Tetraethylammonium, cimetidine, p-aminohippurate, probenecid, amino acids, beta-lactam antibiotic or monocarboxylates did not inhibit the uptake of grepafloxacin and levofloxacin under the same conditions. In conclusion, our results suggested that grepafloxacin and levofloxacin uptakes were mediated by a specific transport system distinct from those for organic cations and anions, amino acids, dipeptides and monocarboxylates.     

特拉唑嗪对左氧氟沙星在大鼠细菌性前列腺炎组织中分布的影响

目的探讨特拉唑嗪对左氧氟沙星在大鼠前列腺炎组织中浓度的影响。方法建立SD雄性大鼠急性细菌性前列腺炎模型96只,随机分为单服左氧氟沙星组和联用特拉唑嗪组,每组48只,分别于给药后0.125、0.25、0.5、1、2、4、8和12h每个时间点活杀6只大鼠,采集2组动物的前列腺制作组织匀浆,HPLC法测定前列腺组织中的左氧氟沙星浓度,3p97软件计算药动学参数。结果单服左氧氟沙星组和联用特拉唑嗪组左氧氟沙星的药-时曲线均为二室模型。主要药动学参数如下:t1/2分别为(4.9±s1.4)和(7.9±2.0)h,tmax分别为(1.4±0.3)和(1.3±0.4)h,ρmax分别为(4.2±1.1)和(7.7±1.7)mg·kg-1,AUC0～12分别为(20±7)和(55±16)mg.h.kg-1。结论特拉唑嗪可提高左氧氟沙星在大鼠前列腺炎组织中的浓度。     

HPLC法测定乳酸左氧氟沙星注射液左氧氟沙星含量

目的建立乳酸左氧氟沙星注射液中左氧氟沙星含量测定方法。方法采用高效液相色谱法,VP-ODS（4.6 mm×150mm,5μm）;流动相：三乙胺磷酸溶液-乙腈（82：18）;流速：1.0 ml·min^-1;柱温：40℃;检测波长为286 nm。供试品溶液制备采用流动相溶解并稀释成每1ml中约含0.1mg的溶液。结果左氧氟沙星线性范围为1.73～15.61 mg·L^-1,平均加样回收率为100.21%。结论本法简捷,快速可靠,可用于控制制剂质量。     

门冬氨酸左氧氟沙星与其他左氧氟沙星盐的药动学比较

目的对门冬氨酸左氧氟沙星与其他左氧氟沙星盐在大鼠体内进行了药动学比较。方法以替硝唑为内标,血浆样品经乙腈沉淀蛋白后,采用高效液相的方法进行了测定。结果线性范围0.5~25μg/m l,日内、间精密度RSD均<6%,平均回收率大于89%。大鼠腹腔注射门冬氨酸左氧氟沙星、盐酸左氧氟沙星、乳酸左氧氟沙星和左氧氟沙星,测定不同时间的药物浓度,所得的主要药物动力学参数:门冬氨酸左氧氟沙星t1/2K a=7.461m in、t1/2α=16.499m in、t1/2β(m in)=218.989m in、tm ax=22.600m in、AUC=1202.262(μg.m in)/m l;盐酸左氧氟沙星t1/2K a=0.064m in、t1/2K e=24.155m in、tm ax=3.433m in、Cm ax=10.946μg/m l、AUC=420.925(μg.m in)/m l;乳酸左氧氟沙星t1/2K a=0.409m in、t1/2K e=13.576m in、tm ax=2.131m in、Cm ax=13.042μg/m l、AUC=282.797(μg.m in)/m l;左氧氟沙星t1/2K a=0.977m in、t1/2K e=8.519m in、tm ax=3.448m in、Cm ax=13.624μg/m l、AUC=221.667(μg.m in)/m l。结论门冬氨酸左氧氟沙星在大鼠体内的生物利用度比左氧氟沙星及其盐有所提高。     

Activity and distribution of histidine decarboxylase and histamine concentration in rat stomach

The involvement of histamine in mediating gastric function under normal and pathological conditions has been largely established. Histidine decarboxylase (HDC) is the only synthetic enzyme of histamine in the mast cell or enterochromaffin like (ECL) cell. In this study, we examined, the activity of HDC by a method based on the modification of Kobayashi's method, the histological distribution of HDC containing cells was determined by an immunohistochemical method and the histamine concentration by a HPLC method in rat stomach. Histamine concentration in the total gastric layer of the fundus is overwhelming large compared to that in the antrum. On the other hand, histamine concentration of the mucosal layer of the fundus is 72.1 +/- 0.4 micrograms/g (mean +/- S.D.) and that in both the muscular and serosal layers is 7.2 +/- 0.4 micrograms/g. HDC activity of the total gastric layer of the fundus was about ten times as high as that in the antrum. Histological distribution of HDC-containing endocrine cells was observed in the basal part of the gastric mucosa of the fundus, but could not be observed in the muscular and serosal layer. These results suggest that HDC-containing endocrine cells, in only the basal parts of the mucosal layer of the fundus, were similar to ECL cells and have important parts for biosynthesis of internal gastric histamine. Therefore, using the total gastric layer of the stomach was thought to be easier than using only the mucosal layer for measuring gastric histamine and HDC-activity in rats.     

甲磺酸左氧氟沙星与左氧氟沙星临床验证比较

目的 :比较甲磺酸左氧氟沙星与左氧氟沙星治疗细菌性感染的有效性和安全性。方法 :采用随机对照试验将 12 6例细菌性感染病人分为甲磺酸左氧氟沙星组和左氧氟沙星组 ,其中甲磺酸左氧氟沙星组 6 3例 ,男性 30例 ,女性 33例 ,年龄 ( 41±s6 )a;左氧氟沙星组 6 3例 ,男性 36例 ,女性 2 7例 ,年龄 ( 40± 9)a。2组分别给予甲磺酸左氧氟沙星片和左氧氟沙星片各 10 0mg ,po,tid ,疗程 7～ 14d。结果 :2组临床总有效率分别为 89% ( 56 /6 3)和 84 %( 53/6 3) ,细菌清除率分别为 89%和 89% ,不良反应发生率分别为 2 1% ( 13/6 3)和 18% ( 11/6 3) ,经统计学处理均差异无显著意义 (P >0 .0 5)。结论 :甲磺酸左氧氟沙星和左氧氟沙星治疗细菌性感染安全、有效     

In silico and in vitro genotoxicity evaluation of levofloxacin n-oxide, an impurity in levofloxacin

Impurities in drug substances and drug products generally do not have beneficial effects and may impose a risk without associated benefit. Levofloxacin n-oxide is an impurity isolated from levofloxacin. However there is insufficient toxic information about levofloxacin n-oxide. This study investigates the genotoxicity of this impurity by in silico and in vitro methods. We used Derek, a commercial structure-activity relationship software package as an in silico tool. The results showed that there was a structural alert (quinolone-3-carboxylic acid or naphthyridine analogue) in this impurity. Then the mouse lymphoma assay (MLA) and chromosome aberration assay in Chinese hamster lung (CHL) cells were conducted in vitro. Both assays were conducted in the presence or absence of S-9 mix. The test impurity was not mutagenic in the test of MLA. While there was a statistically significant increase in the number of metaphase CHL cells with structural aberrations at the concentration of 1 mg/mL with S-9 mix, and the aberrations rate is 6.5%. It did not significantly increase the number of structural aberration in CHL cells in the presence (at other two doses) or absence of S-9 mix. Based on these assays, levofloxacin n-oxide could be controlled as a non-genotoxic impurity despite the DEREK alert for quinolone-3-carboxylic acid or naphthyridine analogue.     

零交导数分光光度法测定乳酸左氧氟沙星葡萄糖注射液中乳酸左氧氟沙星的含量

OBJECTIVETo determine the content Levofloxacin glucose injection. METHODA zero-crossing derivative spectrophotometry method.RESULTSThe calibration curves is linear in the range of 5.0-17.5ug.mL-1(r=0.9998)for Levofloxacin.The average recovery was 100.08%     

Lung tissue distribution after intravenous administration of grepafloxacin: comparative study with levofloxacin

The aim of the present study is to study the pharmacokinetics in plasma, lung lymph and bronchial washing fluid after intravenous infusion of grepafloxacin (GPFX), in comparison with those of levofloxacin (LVFX). Four conscious sheep with chronically instrumented lung lymph fistulas and tracheotomy were prepared. GPFX and LVFX concentrations in plasma and lung lymph after intravenous infusion of the drugs (10 mg/kg) for over 10 min were measured. In addition serial bronchial washing with 50 mL normal saline was performed to obtain epithelial lining fluid (ELF) at 2, 4, 6, 8, 12, 24 h after the intravenous administration. The time courses of lung lymph concentration were almost identical to those of the concomitant levels of both GPFX and LVFX in plasma, suggesting that both GPFX and LVFX could be easily moved from plasma to pulmonary interstitium and/or lung lymph circulation. However, GPFX concentrations of ELF were significantly higher than LVFX concentrations over time after the administration. In addition, intracellular concentrations in ELF of GPFX were also extremely high compared with those of LVFX. These results demonstrated that penetration of GPFX in bronchial wall, bronchial epithelium and/or phagocytic cells was superior to that of LVFX. These observations suggest that the pharmacokinetic characteristics of GPFX in the lung may provide a new insight into the strategy for clinical treatment of various pulmonary infections, especially cytotropic bacterial infections.