诺氟沙星胶囊的实时溶出度监测

目的建立诺氟沙星胶囊的实时溶出度的测定方法,以评价药物的质量。方法采用FODT-601型光纤药物溶出度实时测定仪对4个厂家生产的诺氟沙星胶囊的实时溶出过程进行监测。结果选定290 nm为测定波长,诺氟沙星在20～120μg/ml范围内吸收度值与浓度间的线性关系良好。应用本方法监测的不同厂家诺氟沙星溶出度结果与依照《中华人民共和国药典》2010年版（二部）该制剂规定方法监测结果基本一致,但不同生产厂家的溶出曲线存在一定的差异。结论 FODT-601型光纤药物溶出度实时测定仪可反映药物的真实溶出过程,不需取样分析,减少了操作步骤,测定结果准确。     

诺氟沙星滴入兔眼与注入球结膜下其组织分布及药动学比较

用高效液相色谱法对诺氟沙星点眼与球结膜下注射后眼各组织药物浓度进行测定，比较两种给药途径的眼各组织浓度及其药物动力学参数。结果表明，诺氟沙星点眼与球结膜下注射后４ｈ，泪液诺氟沙星浓度分别为２．０８±０．１９与１６．０７±３．１４μｇ／ｍｌ（Ｐ＜０．０１）；角膜分别为０．７１±０．０７与１．６５±０．２４μｇ／ｇ（Ｐ＜０．０１）。泪液ＡＵＣ分别为９８．３３±７．３１与２７９．８２±３１．７ｈ·μｇ／ｍｌ；角膜ＡＵＣ、Ｃｍａｘ、Ｔｍａｘ、Ｔ１／２Ｋｃ分别为１７．４２±１．２１ｈ·μｇ／ｇ、８．９４±０．８μｇ／ｇ、０．５７±０．０６ｈ、０．９１７±０．１６ｈ与２０．０１±１．０１ｈ·μｇ／ｇ、１０．０５±０．０７μｇ／ｇ、０．４５±０．０５ｈ、１．１５±０．２０ｈ；房水ＡＵＣ、Ｃｍａｘ、Ｔｍａｘ分别为１．１３±０．２１ｈ·μｇ／ｍｌ、０．３９±０．０５μｇ／ｍｌ、０．６２±０．０９ｈ与１．７９±０．０７ｈ·μｇ／ｍｌ、１．００±０．１５μｇ／ｍｌ、０．４７±０．１０ｈ。诺氟沙星点眼与球结膜下注射两种给药途径的上述药动学参数有明显差异（Ｐ＜０．０５或０．０１）。     

脂质饮食对诺氟沙星在Beagle犬体内药动学的影响

目的:研究脂质饮食对诺氟沙星在Beagle犬体内药动学的影响。方法:取6只Beagle犬均分为两组,分别在空腹或进食脂质状态下灌服诺氟沙星胶囊40 mg/kg,2周后两组犬交叉实验;采用高效液相色谱法测定给药前与给药后0.5、1、2、3、4、6、8、10、12、24 h的血药浓度,用3p97软件计算诺氟沙星的药动学参数。结果:诺氟沙星在Beagle犬空腹和进食脂质状态下的药-时曲线均符合一室模型;空腹和进食脂质状态下诺氟沙星的主要药动学参数分别为t1/2(3.82±1.10)、(4.30±1.78)h,tmax(0.72±0.37)、(2.94±1.12)h,cmax(0.93±0.18)、(0.92±0.43)μg/ml,AUC0-24 h(6.26±0.98)、(8.45±1.78)μg·h/ml;两种状态间比较,除tmax差异有统计学意义(P<0.01)外,其余参数差异无统计学意义(P>0.05)。结论:脂质饮食可明显延迟诺氟沙星的达峰时间。     

Selective adsorption of norfloxacin in aqueous media by an imprinted polymer based on hydrophobic and electrostatic interactions

Based on hydrophobic and electrostatic interactions, a norfloxacin (NOF) imprinted polymer (P1) was prepared by the combined use of bismethacryloyl-beta-cyclodextrin (BMA-beta-CD) and 2-(diethylamino)ethylmethacrylate (DEAEM) as functional monomers. Compared with the molecularly imprinted polymers (MIPs) using only BMA-beta-CD or DEAEM as a functional monomer, P2 and P3, respectively, P1 showed higher binding affinity and specificity for NOF in aqueous media. Scatchard plot analysis revealed that two classes of binding sites were formed in the imprinted polymer with dissociation constants of 0.32 micromol/ml and 1.19 micromol/ml, respectively. It demonstrated that the combination of hydrophobic effect and electrostatic interaction in molecular imprinting was essential for the improvement of the selective ability of the imprinted polymer. Factors that influenced rebinding of the imprinted polymer including pH, water content in the adsorbed solution were explored.     

诺氟沙星-磺丁基醚-β-环糊精包合物的制备及人体药动学研究

目的：制备诺氟沙星（NFX）-磺丁基醚-β-环糊精（SBE-β-CD）包合物,并研究其溶解度、溶出度以及体内药动学行为。方法：采用冷冻干燥法制备NFX—SBE-β-CD包合物,以X-射线衍射法及差示热量扫描法（DSC）对其进行物相鉴定。同时,测定NFX包合物的溶解度、溶出度并研究其体内药动学。结果：NFX与SBE—β—CD已形成包合物;经包合后,NFX的溶解度、溶出速率显著增加;包合物的药动学参数t1/2,tmax与原药比较,无显著性差异（P〉0．05）,而其尿药排泄速率以及累积排泄量均显著高于原药（P〈0．05）。结论：NFX制成SBE-β-CD包合物后,其溶解度、溶出度以及体内生物利用度显著改善。     

Effects of norfloxacin and butylated hydroxyanisole on the freshwater microalga Scenedesmus obliquus

The toxic effects of norfloxacin (NOR) and butylated hydroxyanisole (BHA) on the microalga Scenedesmus obliquus were assessed in terms of growth rate, concentration of chlorophyll a, activities of 7-ethoxyresorufin-o-dealkylases (EROD), glutathione s-transferase (GST), catalase (CAT) and total malondialdehyde content (MDA). The 96 h EC₅₀ was 38.49 and 11.12 mg/l for NOR and BHA, respectively. Growth of S. obliquus was affected slightly under low concentrations of BHA (<4 mg/l) and NOR (<15 mg/l) over the 96 h exposure period. With the increasing concentrations of these two compounds, growth of S. oblique decreased significantly. Growth inhibition was 82.4% at 60.0 mg/l for NOR and 60.6% at 16.0 mg/l for BHA after 96 h. A similar trend was also observed for chlorophyll a. NOR and BHA affected Phase I and Phase II enzyme activities differently. Upon exposure to NOR, EROD was induced at concentration <15.0 mg/l and depressed at concentrations >30 mg/l significantly. CAT and GST exhibited similar trends during the exposure period. Compared to controls, MDA content only showed high induction at high concentrations of NOR (>30 mg/l). However, EROD activity did not display any change compared to control responses during BHA exposure, whereas GST showed significant induction for all concentrations over the exposure period. CAT activity showed induction at low concentration and depression at high concentration. MDA content increased with the rise of BHA during the exposure period. These types of assays, revealing toxic effects of NOR and BHA to phototrophs, could be employed to assess the potential risks of these xenobiotics to aquatic ecological systems.     

Norfloxacin-Poly(l-Lysine Citramide Imide) Conjugates and Structure-dependence of the Drug Release

Norfloxacin (Nflx), an antibiotic which is active against some intracellular bacteria, was coupled to a polymeric carrier, namely poly(_l-lysine citramide) via a lysine or an ethylcarbamate spacer to obtain a macromolecular prodrug. The carrier, which derived from the two metabolites citric acid and _l-lysine, is known to be biocompatible and slowly degradable under slight acidic conditions. Conjugates were characterised by UV, ¹H and ¹³C NMR and SEC. The presence of Norfloxacin and the lysine type spacer caused chain aggregation, due to a probable physical cure. The release of Norfloxacin from these prodrugs and from a prodrug where Norfloxacin is bound to the carrier backbone without spacer arm was investigated comparatively in vitro. Conjugation via a carbamate-type linkage appeared as a method to achieve the release of Norfloxacin from a PLCA-type conjugate at neutral.     

Spectrophotometric determination of some fluoroquinolone antibacterials by binary complex formation with xanthene dyes

Two simple, rapid and sensitive spectrophotometric methods for the determination of levofloxacin, norfloxacin and ciprofloxacin have been performed in pure form, pharmaceutical tablets and spiked human urine. Both methods are based on the formation of a binary complex between the drugs and one of the two xanthene dyes, eosin Y or merbromin in aqueous buffered medium. Under the optimum conditions, the binary complexes showed absorption maxima at 547 nm for eosin Y and 545 nm for merbromin. Using eosin Y, the calibration graph was linear over the range 2-8 microg ml(-1) for the three drugs with mean percentage recoveries 99.935 +/- 0.648, 99.973 +/- 0.678 and 100.011 +/- 0.606 for levofloxacin, norfloxacin and ciprofloxacin, respectively. While in case of merbromin, the concentration range was 2-15 microg ml(-1) with mean percentage recoveries 99.960 +/- 0.491, 100.017 +/- 0.510 and 99.980 +/- 0.506 for the three drugs, respectively. The proposed methods were successfully applied to determine these drugs in their tablet formulations and spiked human urine and the results compared favorably to that of reference methods. The suggested methods have the advantage of being applicable for the determination of the three drugs without prior extraction. They are recommended for quality control and routine analysis where time, cost effectiveness and high specificity of analytical techniques are of great importance.     

口服氢氧化铝对静注诺氟沙星体内药动学的影响

利用紫外分光光度法测定家兔血中的诺氟沙星浓度,对静注诺氟沙星在口服铝盐前后的体内药动力学的情况进行了研究。结果显示单独静注诺氟沙星与同时口服铝盐两种方案给药的药动学参数无显著性差异。本实验为临床合理用药提供了参考资料。     

4种抗菌药物对淋球菌体外抗菌活性的研究

本文采用琼脂倍比稀释法检测38株淋球菌对4种抗菌药物的敏感性,并作β-内酰胺酶测定.结果表明,21.1%的菌株对青霉素耐药;7.9%的菌株为PPNG;7.9%的菌株对壮观霉素耐药;而100%的菌株对氟嗪酸、氟哌酸敏感,且MIC_(50)、MIC_(90)值均低.结果显示,应注意淋球菌对青霉素、壮观霉素的耐药性,推荐用氟嗪酸、氟哌酸治疗淋病