国产氟罗沙星体外抗菌活性研究

测定国产氟罗沙星对４９３株临床分离细菌的最低抑菌浓度（ＭＩＣ），并与氧氟沙星、洛美沙星、环丙沙星和几种头孢菌素、氨基糖苷类抗生素作了比较。结果表明：氟罗沙星对革兰氏阴性细菌有强大抗菌活性，对肠杆菌科细菌的ＭＩＣ９０≤１μｇ／ｍｌ。对铜绿假单胞菌亦有较强抗菌活性，其ＭＩＣ５０、ＭＩＣ９０分别为２和４μｇ／ｍｌ。金葡球菌（含ＭＲＳＡ菌株）对氟罗沙星亦很敏感，ＭＩＣ９０≤１μｇ／ｍｌ。链球菌属对其基本耐药，ＭＩＣ９０为８～１６μｇ／ｍｌ。对大多数常见致病菌，氟罗沙星体外抗菌活性与氧氟沙星、洛美沙星相近，稍逊于环丙沙星。对革兰氏阴性菌，氟罗沙星与头孢噻肟、头孢他啶、阿米卡星相当，优于头孢唑林、氨苄西林、哌拉西林、庆大霉素。耐庆大霉素、头孢菌素菌株对氟罗沙星仍敏感。细菌对氟罗沙星单步自发耐药突变频率极低，但通过连续传代培养可以培育出对氟罗沙星高度耐药菌株。     

国产氟罗沙星葡萄糖注射液的临床评价

国产氟罗沙星静滴治疗１０２名呼吸道、泌尿道、消化道和皮肤软组织感染患者，总的临床有效率为９５．１０％（９７／１０２），细菌清除率为９４．６８％（８９／９４）。不良反应轻微，不影响继续治疗，不良反应发生率为８．８２％。同时以氧氟沙星为对照药，在呼吸道和泌尿道感染中进行了随机对照实验，氟罗沙星组６２例，氧氟沙星组６０例，两组的临床和细菌学疗效及不良反应发生率相似。并对１２５株临床分离菌测定了氟罗沙星和氧氟沙星的ＭＩＣ，结果显示氟罗沙星对肠杆菌科细菌和葡萄球菌属具有高度的抗菌活性，对假单胞菌也有良好的活性。     

健康人单次口服国产氟罗沙星的药物动力学研究

健康人单次口服国产氟罗沙星的药物动力学研究李可欣，孙春华，刘蕾，付得兴，缪竞智（北京医院，北京１００７３０）１０例健康志愿者单次口服４０Ｏｍｇ氟罗沙星后的药物动力学。其血清及尿中的氟罗沙星浓度均采用微生物及ＨＰＬＣ两种方法进行测定。药物浓度数据采用３...     

氟罗沙星的诱变性研究

用鼠伤寒沙门氏菌／微粒体致突变试验（Ａｍｅｓ试验）研究国产氟罗沙星的诱变性表明：氟罗沙星诱导ＴＡ_（１０２）菌株回变数显著增高，并且其回变数与药物剂量之间存在着相关性，其最高回变数为自发回变数的两倍以上；但对ＴＡ_（９７）、ＴＡ_（９８）、ＴＡ_（１００）菌株，未引起回变数的增加。结果揭示，氟罗沙星在细菌检测系统中存在诱变活性。     

喹诺酮类药物对厌氧菌的体外抗菌活性研究

用６种喹诺酮类药物（氟罗沙星、诺氟沙星、依诺沙星、环丙沙星、洛美沙星、氧氟沙星）对９３株不同厌氧菌作体外抗菌活性研究，并与常用的抗厌氧菌药物克林霉素、甲硝唑比较，结果显示环丙沙星对厌氧菌的抗菌活性最强，与甲硝唑类似，优于克林霉素；其次为氧氟沙星和氟罗沙星；洛美沙星、依诺沙星、诺氟沙星效果较差。其中，革兰氏阳性厌氧菌对环丙沙星最敏感，其次为氟罗沙星和氧氟沙星；革兰氏阴性厌氧菌对环丙沙星最敏感，其次为     

氟罗沙星的诱发性研究

用鼠伤寒沙氏门氏菌／微粒体致突变试验（Ａｍｅｓ试验）研究国产氟罗沙星的诱变性表明：氟罗沙星诱导ＴＡ１０２菌株回变数显著增高，并且其回变数与药物剂量之间存在着相关性，其最高回变数为自发回变数的两倍以上，但对ＴＡ９７，ＴＡ９８，ＴＡ１００菌株，未引起回变数的增加，结果揭示，氟罗沙星在细菌检测系统中存在诱变活性。     

乳酸氟罗沙星葡萄糖注射液的配制及含量测定

氟罗沙星为第四代喹诺酮类抗生素，具有抗菌谱广、抗菌作用强、长效的特点。为方便临床使用，我们配制了氟罗沙星葡萄糖注射液，并用分光光度法进行了含量测定。操作简便，结果准确。氟罗沙星的回收率均１００．０８％，ＲＳＤ＝０．０３２％。     

氟罗沙星的致癌研究

应用哺乳动物细胞转化试验，对国产氟罗沙星进行了致癌性研究。结果在ＢＡＬＢ／３Ｔ３细胞转化试验中，氟罗沙星未诱发细胞形态学的改变。结果提示氟罗沙星无体外致癌性。     

氟罗沙星的药理与临床

1前言自1962年，第一个隆诺酮抗菌药萘啶酸（nalidixicacid）用于临床以来，此类化合物中各具特点的衍生物如奥索利酸（。x。1血沁acid），西诺沙星（cinoxacin），诺氟沙星（nor－H。x。dn，1986年），环丙沙星kWr。n。xZcln，1987年），氧氟沙星，（ofloxacin，1990年），替马沙星Oemafloxacin，1992年），依诺沙星（eno－xacin）（1992年），洛美氟按星（lomefloxacin1992年）等相继问世，并已用于临床，取得了较好的治疗效果。本文拟对新近使用的氟罗沙星Olero。ci…作一简要介绍。2抗菌作用特点氛罗沙星具有抗菌谱广，抗菌活性高的特…     

鲁抗集团研制成功国家四类新药氟罗沙星葡萄糖注射液

由山东鲁抗医药集团辰欣公司与南京晟翔医药化工研究所联合研制的国家四类新药氟罗沙星葡萄糖注射液日前获得国家药品监督管理局新药证书及生产批准文号。 氟罗沙星葡萄糖注射液为广谱、长效、新型喹诺酮类抗菌药物,对革兰阳性菌、阴性菌及部分厌氧菌等有     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.