甲氧基红霉素对卡马西平药物动力学的影响

应用荧光偏振免疫法，测定６只家兔ｐｏ卡马西平及连续多次ｐｏ用搓甲氧基红霉素后ｐｏ卡马西平的血清卡马西平浓度，用３ｐ８７程序包按二室模型对数据进行处理并进行统计学分析。     

Clinical and bacteriological outcomes in hospitalised patients with community-acquired pneumonia treated with azithromycin plus ceftriaxone, or ceftriaxone plus clarithromycin or erythromycin: a prospective, randomised, multicentre study

This study compared patients with moderate-to-severe community-acquired pneumonia (CAP) requiring hospitalisation, who received initial therapy with either intravenous ceftriaxone plus intravenous azithromycin, followed by step-down to oral azithromycin (n = 135), with patients who received intravenous ceftriaxone combined with either intravenous clarithromycin or erythromycin, followed by step-down to either oral clarithromycin or erythromycin (n = 143). Clinical and bacteriological outcomes were evaluated at the end of therapy (EOT; day 12-16) or at the end of study (EOS; day 28-35). At baseline, mean APACHE II scores were 13.3 and 12.6, respectively, with >50% of patients classified as Fine Pneumonia Severity Index (PSI) category IV or V. Clinical success rates (cure or improvement) in the modified intent-to-treat (MITT) population at EOT were 84.3% in the ceftriaxone/azithromycin group and 82.7% in the ceftriaxone/clarithromycin or erythromycin group. At EOS, MITT success rates (cure only) were 81.7% and 75.0%, respectively. Equivalent success rates in the clinically evaluable population were 83% and 87%, respectively, at EOT, and 79% and 78%, respectively, at EOS. MITT bacteriological eradication rates were 73.2% and 67.4%, respectively, at EOT, and 68.3% vs. 60.9%, respectively, at EOS. Mean length of hospital stay (LOS) was 10.7 and 12.6 days, and the mean duration of therapy was 9.5 and 10.5 days, respectively. The incidence of infusion-related adverse events was 16.3% and 25.2% (p 0.04), respectively. An intravenous-to-oral regimen of ceftriaxone/azithromycin was at least equivalent in efficacy and safety to the comparator regimen and appeared to be a suitable treatment option for hospitalised patients with CAP.     

药敏纸片的质量控制研究

目的：探讨和研究药敏纸片质量控制的方法。方法：以克拉霉素药敏纸片为例，参照美国临床实验室标准化委员会(NCCLS)和联邦法规全书(CFR)的方法，建立一套药敏纸片质量控制的指标，包括鉴别、检查及含量测定。结果：采用专属性较强、灵敏度较高的TLC法进行鉴别，最低检出量为50μg；制订纸片的的直径、重量差异、含量均匀性及干燥失重作为检查项，采用短小芽孢杆菌(Bacillus pumilus)[CMCC(B)63202]作为检定菌，进行含量测定。结论：建立的克拉霉素药敏纸片质量标准能够控制其质量，可作为其他抗生素药敏纸片建立质量标准的参考。     

克拉霉素的极谱催化波及其应用

目的建立灵敏快速测定克拉霉素的新方法。方法基于氧化剂存在时克拉霉素产生的极谱催化波,用线性单扫描极谱法快速测定克拉霉素。结果在0.24 mol·L^-1 KH₂PO₄-Na₂HPO₄ (pH 6.81)支持电解质中，克拉霉素于-0.79 V (vs SCE)电位处产生1个还原波。加入过二硫酸钾后，该还原波峰电流增加约20倍，峰电位基本不变，产生一极谱催化波。其二阶导数峰电流i_p″与克拉霉素的浓度在4.0×10^-7-5.0×10^-5mol·L^-1呈良好线性关系(r=0.999 1,n=10)，检出限为2.0×10^-7 mol·L^-1。结论该方法可用于药剂中克拉霉素含量的测定。     

克拉霉素片人体药动学及相对生物利用度研究

 目的：研究克拉霉素片在健康人体内的药动学与相对生物利用度。方法：采用高效液相色谱法测定8名志愿者单剂量po500mg不同厂家产克拉霉素片后的血药浓度变化情况，计算两者的药动学参数及相对生物利用度，以AUC_0→∞，t_max，c_max为指标，配对t检验法分析两厂产克拉霉素片的生物等效性。结果：二者药-时曲线可用二室模型拟合，其：t_1/2(β)分别是3.04h和3.91h，t_max分别是1.94h和1.92h，c_max分别是2.34μg·ml^-1和2.27μg·ml^-1,AUC_0→∞分别是13.66μg·h·ml^-1和14.44μg·h·ml^-1。配对ｔ检验结果表明，两厂产品的AUC_0→∞，c_max，t_max均无显著性差异(P>0.05)。结果：两厂家产克拉霉素片为生物等效制剂，A药对B药的相对生物利用度为95.3%。     

莫西沙星治疗慢性支气管炎急性发作的前瞻性研究

目的:研究莫西沙星对慢性支气管炎急性发作(AECB)的疗效.方法:对AECB患者随机分成二组,一组口服莫西沙星400mg,gd×6d,另一组口服克拉霉素500mg,bid×6d,观察临床疗效和细菌清除状况以及不良反应.结果:莫西沙星治疗组和克拉霉素治疗组病人的临床总有效率分别为93.1%和87.9%,差异无显著性(P＞0.05);支气管周围炎症吸收率分别为84.7%和71.2%,差异有显著性(P＜0.05);痰中致病菌清除率分别为88.9%和72.1%,差异有显著性(P＜0.05);不良反应发生率分别为1.4%和13.6%,差异有显著性(P＜0.05).结论:在治疗AECB时,莫西沙星与克拉霉素比较,两者的临床疗效基本相似,但其支气管周围炎症吸收状况前者优于后者,痰中致病菌清除率更高,更具依从性和耐受性.     

幽门螺杆菌的耐药分析及对Hp根除的影响

目的探讨幽门螺杆菌(Hp)对常用抗菌药的耐药性及对Hp根除的影响,给临床提供合理用药的科学依据.方法采用用改良布氏活性炭培养基(平板)在微需氧环境中培养幽门螺杆菌,并利用琼脂稀释法行幽门螺杆菌的药敏试验.并用三联疗法对62例消化性溃疡进行Hp根除治疗.结果从112例消化性溃疡患者胃黏膜中培养出Hp 62株,对阿莫西林、四环素、克拉霉素、甲硝唑、替硝唑、呋喃唑酮的耐药率分别为1.61%、3.23%、11.2%、58.1%、3.23%、0%.7d根除治疗对Hp的总根除率为:对甲硝唑及克拉霉素敏感株根除率为91.5%,对甲硝唑耐药株根除率为52%,对克拉霉素耐药株根除率为0(P＞0.05).结论阿莫西林、替硝唑、四环素、呋喃唑酮的耐药率较低;而甲硝唑和克拉霉素耐药率较高.其耐药影响Hp根除.     

Current recommendations for Helicobacter pylori therapies in a world of evolving resistance

Occurrence of resistance, especially to clarithromycin, renders the standard triple therapy used to cure Helicobacter pylori infection ineffective. This review presents the bacteriological and pharmacological basis for H. pylori therapy and the current recommendations. The third-line treatment must be based on clarithromycin susceptibility testing. If the bacteria are still susceptible, failure may come from problems of compliance, hyperacidity or high bacterial load which can be overcome. If the bacteria are resistant, different regimens must be considered, including bismuth and non-bismuth-based quadruple therapies (sequential or concomitant), as well as triple therapies where amoxicillin is administered several times a day to obtain an optimal concentration at the gastric mucosal level. The treatments are becoming more and more complex and ecologically unsatisfactory, waiting for new agents or vaccines.     

Development of a predictive in vitro dissolution for clarithromycin granular suspension based on in vitro-in vivo correlations

The objective of this study was to evaluate the in vitro behavior of different clarithromycin granular suspensions based on a developed in vitro-in vivo correlation model, using one reference and two test formulations. In vitro release rate data were obtained for each product using the USP apparatus II, operated at 50?rpm under different pH conditions. The dissolution efficiency was used to analyze the dissolution data. In vivo study was performed on six healthy male volunteers under fasting condition. Correlation was made between in vitro release and in vivo absorption. A linear model was developed using percent absorbed data versus percent dissolved data from the three products. Dissolution condition of 0.1N HCl for 1?h and then phosphate buffer at pH 6.8 was found to be the most discriminating dissolution method. Rate of absorption for the reference as estimated by Wagner-Nelson deconvolution was correlated with in vitro release with a correlation coefficient of 0.99. The in vivo results for the two test products were compared to the predicted values using the reference model with a correlation coefficient of 0.94. Furthermore, multiple level C correlations were obtained for some pharmacokinetic parameters with the corresponding in vitro kinetic parameters with correlation coefficients exceeding 0.90. Moreover, the interpretation of the in vitro and in vivo data with reference to formulations was discussed.