Clarithromycin suppresses the periodontal bacteria-accelerated abdominal aortic aneurysms in mice

Aoyama N, Suzuki J‐I, Ogawa M, Watanabe R, Kobayashi N, Hanatani T, Yoshida A, Ashigaki N, Izumi Y, Isobe M. Clarithromycin suppresses the periodontal bacteria‐accelerated abdominal aortic aneurysms in mice. J Periodont Res 2012; 47: 463–469. © 2011 John Wiley & Sons A/S Background and Objective: Although clarithromycin (CAM) has many biological functions, including regulation of MMPs, little is known about its effect on abdominal aortic aneurysms. Periodontopathic bacteria have been reported to be associated with several kinds of circulatory diseases. The purpose of this study was therefore to clarify the effect of CAM on periodontopathic bacteria‐accelerated abdominal aortic aneurysms. Material and Methods: Abdominal aortic aneurysm was produced in mice by the peri‐aortic application of 0.25 m CaCl₂. The mice were inoculated once per week with live Porphyromonas gingivalis, which is one of the major periodontopathic bacteria. Test mice (n = 8) were given a daily oral dose of CAM, while control mice (n = 13) were not. Results: Four weeks after the operation, the P. gingivalis‐injected and CAM‐treated mice showed a significant decrease in the aortic diameter in comparison with the mice only injected with P. gingivalis. Histopathologically, the samples obtained from the P. gingivalis‐injected and CAM‐treated mice showed less elastic degradation. Moreover, the plasma MMP‐2 concentration of the CAM‐treated mice decreased significantly. Conclusion: These findings suggest that CAM administration is useful to suppress periodontal bacteria‐accelerated abdominal aortic aneurysms via MMP regulation.     

Stabilization Mechanism of Roxithromycin Tablets Under Gastric pH Conditions

Macrolide antibiotics are widely used at clinical sites. Clarithromycin (CAM), a 14-membered macrolide antibiotic, was reported to gelate under acidic conditions. Gelation allows oral administration of acid-sensitive CAM without enteric coating by hindering the penetration of gastric fluid into CAM tablets. However, it is unknown whether this phenomenon occurs in other macrolide antibiotics. In this study, we examined the gelation ability of 3 widely used macrolide antibiotics, roxithromycin (RXM), erythromycin A, and azithromycin. The results indicated that not only CAM but also RXM gelated under acidic conditions. Erythromycin A and azithromycin did not gelate under the same conditions. Gelation of RXM delayed the disintegration of the tablet and release of RXM from the tablet. Disintegration and release were also delayed in commercial RXM tablets containing disintegrants. This study showed that 2 of the 4 macrolides gelated, which affects tablet disintegration and dissolution and suggests that this phenomenon might also occur in other macrolides.     

克拉霉素与头孢呋辛联合应用对肺炎链球菌和金黄色葡萄球菌的体内抗生素后效应

目的：探讨克拉霉素（CLA）与头孢呋辛（CEFU）联合应用对肺炎链球菌和金黄色葡萄球菌的体内抗生素后效应（PAE）。方法：采用琼脂平板倍比稀释法和棋盘法分别测定CLA、CEFU单用及联用时对肺炎链球菌、金黄色葡萄球菌的最小抑菌浓度（MIC）,并计算联合指数（FIC）;建立小鼠股部肺炎链球菌、金黄色葡萄球菌感染模型,并且应用平板菌落计数法测定CLA与CEFU单用及联合应用对肺炎链球菌、金黄色葡萄球菌的体内PAE。结果：CLA、CEFU单用及联用均对肺炎链球菌、金黄色葡萄球菌产生一定的PAE;两者联用的PAE长于单用时的PAE,呈浓度依赖性,联用后对肺炎链球菌体内PAE表现为相加或无关作用,对金黄色葡萄球菌体内PAE表现为无关作用。结论：CLA与CEFU联用能延长CLA、CEFU单用时的PAE。     

Involvement of intestinal permeability in the oral absorption of clarithromycin and telithromycin

The involvement of intestinal permeability in the oral absorption of clarithromycin (CAM), a macrolide antibiotic, and telithromycin (TEL), a ketolide antibiotic, in the presence of efflux transporters was examined. In order independently to examine the intestinal and hepatic availability, CAM and TEL (10 mg/kg) were administered orally, intraportally and intravenously to rats. The intestinal and hepatic availability was calculated from the area under the plasma concentration–time curve (AUC) after administration of CAM and TEL via different routes. The intestinal availabilities of CAM and TEL were lower than their hepatic availabilities. The intestinal availability after oral administration of CAM and TEL increased by 1.3‐ and 1.6‐fold, respectively, after concomitant oral administration of verapamil as a P‐glycoprotein (P‐gp) inhibitor. Further, an in vitro transport experiment was performed using Caco‐2 cell monolayers as a model of intestinal epithelial cells. The apical‐to‐basolateral transport of CAM and TEL through the Caco‐2 cell monolayers was lower than their basolateral‐to‐apical transport. Verapamil and bromosulfophthalein as a multidrug resistance‐associated proteins (MRPs) inhibitor significantly increased the apical‐to‐basolateral transport of CAM and TEL. Thus, the results suggest that oral absorption of CAM and TEL is dependent on intestinal permeability that may be limited by P‐gp and MRPs on the intestinal epithelial cells. Copyright © 2014 John Wiley & Sons, Ltd.     

Inhibitory effects of aspirin and indometacin on the growth of Helicobacter pylori in vitro

OBJECTIVE: The interactions between non‐steroidal anti‐inflammatory drugs and Helicobacter pylori have not been sufficiently documented to date. The aim of this study was to investigate the possible effects of aspirin and indometacin on the growth of H. pylori and to determine the effects of aspirin on the susceptibility of H. pylori to some antimicrobials. METHODS: Kinetic studies were performed by inoculating strains of H. pylori in brucella broth with different concentrations of aspirin and indometacin. Growth of bacteria in the broth was assessed spectrophotometrically and by viable colony counts after incubation for 24 and 48 h. Bacterial morphology was determined by Gram stain under light microscopy. The minimal inhibitory concentration (MIC) of aspirin and indometacin was determined by the standard agar dilution method. The MIC of amoxicillin, clarithromycin and metronidazole was measured in the presence and absence of aspirin by the E‐test method. RESULTS: Kinetic studies revealed that aspirin and indometacin inhibited the growth of H. pylori in a dose‐dependent manner. The bactericidal activity of these agents was expressed by cell lysis. Aspirin at 400 µg/mL produced an almost 2‐log decrease in the number of CFU/mL at 48 h. Similar inhibitory effects were obtained when 100 µg/mL indometacin was tested. The MIC at which 90% of H. pylori was inhibited was 512 µg/mL and 128 µg/mL for aspirin and indometacin, respectively. Increased susceptibility of H. pylori to amoxicillin, clarithromycin and metro­nidazole was found in the presence of aspirin. CONCLUSIONS: Aspirin and indometacin could significantly inhibit the growth of H. pylori when incubated in brucella broth in vitro. A subinhibitory concentration of aspirin enhanced the susceptibility of H. pylori to some antimicrobial agents.     

Clinical characteristics and early outcomes of patients newly diagnosed with pulmonary Mycobacterium avium complex disease

Background

The incidence of asymptomatic pulmonary Mycobacterium avium complex (MAC) disease appears to be increasing. This study aimed to determine the clinical characteristics and examine early outcomes of patients newly diagnosed with MAC disease.

克拉霉素联合桉柠蒎治疗鼻窦炎的临床效果及对血清炎症因子水平的影响

目的探究克拉霉素联合桉柠蒎治疗鼻窦炎的临床效果及对血清炎症因子水平的影响。方法选择我院收治的78例鼻窦炎患者作为研究对象,按照随机抽签法将其分为观察组(39例,克拉霉素+桉柠蒎)和参照组(39例,克拉霉素)。比较两组患者的治疗效果。结果观察组的治疗总有效率明显高于参照组(P<0.05)。治疗后,两组的IFN-γ、IL-1β、TNF-α、IL-10水平均降低,且观察组明显低于参照组(P<0.05)。治疗后,两组的CCCRC评分均升高,RSOM-31评分均降低,且观察组明显优于参照组(P<0.05)。结论克拉霉素联合桉柠蒎治疗鼻窦炎的临床效果显著,可促使患者炎症反应减轻,改善嗅觉功能及生活质量。     

Controlling acute bacterial maxillary sinusitis

In acute maxillary sinusitis, after an initial viral episode, bacterial infection can be demonstrated using specific investigations and bacterial isolation. In the vast majority of cases, however, the diagnosis is presumptive. Symptomatic treatments tend to reduce pain and inflammation for easier pus drainage. The decision for or against antibiotic therapy continues to be a matter of debate. Many antibiotics have been used but modern guidelines have established recommendations for the choice and duration of treatments, based on (i) knowledge of pathogens and of their resistance profiles; (ii) improved understanding of the pharmacology of antibiotics, guiding doses and administration routes; (iii) comparative double-blind studies, evaluating antibiotics versus placebo and β-lactams versus macrolides. Use of newer drugs (fluoroquinolones, ketolides) must be discussed in terms of cost and efficacy.     

奥红胶囊质量标准研究

目的建立奥红胶囊的质量标准。方法采用TLC和HPLC的方法对胶囊中奥美拉唑和克拉霉素进行定性研究。含量测定采用反相高效液相色谱法(RP-HPLC),色谱柱为ZorbaxODS C18柱(150 mm×4.6 mm,5μm),克拉霉素以乙腈-磷酸盐缓冲液(0.069 moL.L-1磷酸二氢钾,pH 5.5,2 mL三乙胺)(50∶50)为流动相,检测波长:210 nm,柱温:40℃,流速1mL.min-1;奥美拉唑以乙腈-磷酸盐缓冲液(0.02 moL.L-1磷酸二氢钾,pH4.5)(30∶70)为流动相,检测波长302 nm,柱温:25℃,流速1 mL.min-1。结果确定了克拉霉素和奥美拉唑的定性和定量方法。结论试验中所采用方法快速、灵敏、准确,可为奥红胶囊的质量评价提供有效手段。     

LC-MS/MS法测定克拉霉素血浓度及药动学

目的建立测定人血浆中克拉霉素的LC-MS／MS法，研究市售克拉霉素胶囊在人体的药动学特点。方法以罗红霉素为内标，取血浆样品0．3mL经蛋白沉淀后，以甲醇-水（1％甲酸溶液）-乙腈=（80：10：10）为流动相，用C18柱分离，采用电喷雾离子源，正离子方式检测，扫描方式为多反应检测（MRM）。结果克拉霉素线性范围为10～2500μg·L^-1，日内、日间RSD均〈3．5％。应用此法研究18名健康受试者单剂量口服250mg克拉霉素市售胶囊的药动学参数tmax、ρmax、t1/2、AUC0→t和AUC0→∞，其值分别为（1．95±0．71）h、（949±399）μg·L^-1、（4．79±0．84）h、（5600±1753）μg·h·L^-1、（5766±1776）μg·h·L^-1。结论该法用于人体药动学的研究具有专属、快速、灵敏等特点。