Shinkai I, Ohta Y
Merck Research Laboratories, Rahway NJ 07065-0900, USA.
Bioorg Med Chem. 1996 Apr;4(4):521-2. doi: 10.1016/0968-0896(96)00052-1.
Dirithromycin is a semisynthetic derivative of erythromycin, a 14-membered ring macrolide antibiotic. The drug is converted during absorption and distribution, to an active metabolite 9-(S)-erythromycylamine, which is the predominant compound found in plasma and extravascular tissues. High tissue concentration of erythromycylamine is achieved after oral doses of dirithromycin, with slow release back into the circulation. The mechanism of action of dirithromycin is like that of erythromycin and other macrolides. These compounds inhibit RNA-dependent protein synthesis. It has recently been suggested that all macrolides stimulate dissociation of peptidyl-tRNA from ribosomes during the elongation phase, leading to inhibited protein synthesis. The antimicrobial spectrum of dirithromycin is similar to that of erythromycin, although the drug offers no significant advantage with regard to MIC values. In vitro against Gram-positive isolates, dirithromycin exhibits similar potency to that of clarithromycin, erythromycin, roxithromycin, and clindamycin. In vivo, dirithromycin is active against penicillin-susceptible Staphylococcus aureus, beta-hemolytic streptococci, and Streptococcus pneumoniae. Dirithromycin is as effective as penicillin VK against streptococcal pharyngitis and tonsilitis, and as effective as erythromycin against acute superimposed chronic bronchitis and skin and soft-tissue infections. In comparison with other newer macrolides, dirithromycin has shown similar or lesser in vitro activity. In particular, Haemophilus influenzae, Bacteroides spp., Peptococcus-Peptostreprococcus spp., Clostridium perfringens, Legionella spp., Neisseria gonorrhoeae, and Chlamydia trachomatis were all less sensitive to dirithromycin than azithromycin or clarithromycin. Once-daily oral administration of dirithromycin (500 mg) has been demonstrated to be similar in efficacy to erythromycin (250 mg, 4 times daily), each for approximately 7 days, in the treatment of acute bronchitis or acute-exacerbations of chronic bronchitis in controlled studies. Proven or presumed pathogen eradication rates were 83 and 86% for acute bronchitis patients treated with dirithromycin and erythromycin, respectively. Corresponding bacteriological response rates in acute exacerbations of chronic bronchitis were 75 to 84% with dirithromycin and 75 to 82% with erythromycin. Both agents achieved clinical cure or improvement in over 85% of the patients with either condition. The main advantage of dirithromycin over erythromycin appears to be once-daily administration. Lilly launched dirithromycin in September 1993, in Spain, received approval from FDA in August 1995, and launched it during October 1995.
地红霉素是红霉素的半合成衍生物，红霉素是一种14元环大环内酯类抗生素。该药物在吸收和分布过程中转化为活性代谢产物9-(S)-红霉素胺，这是在血浆和血管外组织中发现的主要化合物。口服地红霉素后可在组织中达到较高浓度，并缓慢释放回循环系统。地红霉素的作用机制与红霉素和其他大环内酯类药物相似。这些化合物抑制依赖RNA的蛋白质合成。最近有人提出，所有大环内酯类药物在延伸阶段都会刺激肽基-tRNA从核糖体上解离，从而导致蛋白质合成受到抑制。地红霉素的抗菌谱与红霉素相似，尽管该药物在最低抑菌浓度值方面没有显著优势。在体外，地红霉素对革兰氏阳性菌的抗菌活性与克拉霉素、红霉素、罗红霉素和克林霉素相似。在体内，地红霉素对青霉素敏感的金黄色葡萄球菌、β-溶血性链球菌和肺炎链球菌具有活性。地红霉素在治疗链球菌性咽炎和扁桃体炎方面与青霉素V钾一样有效，在治疗急性叠加慢性支气管炎以及皮肤和软组织感染方面与红霉素一样有效。与其他新型大环内酯类药物相比，地红霉素的体外活性相似或较低。特别是，流感嗜血杆菌、拟杆菌属、消化球菌-消化链球菌属、产气荚膜梭菌、军团菌属、淋病奈瑟菌和沙眼衣原体对地红霉素的敏感性均低于阿奇霉素或克拉霉素。在对照研究中，每日一次口服地红霉素（500mg）已被证明在治疗急性支气管炎或慢性支气管炎急性加重方面与红霉素（250mg，每日4次）疗效相似，疗程均约为7天。接受地红霉素和红霉素治疗的急性支气管炎患者的病原菌清除率分别为83%和86%。在慢性支气管炎急性加重患者中，地红霉素和红霉素的相应细菌学反应率分别为75%至84%和75%至82%。两种药物对超过85%的两种疾病患者均实现了临床治愈或改善。地红霉素相对于红霉素的主要优势似乎是每日一次给药。礼来公司于1993年9月在西班牙推出地红霉素，1995年8月获得美国食品药品监督管理局批准，并于1995年10月上市。
