Shain Christopher S, Amsden Guy W
Clinical Pharmacology Research Center, Bassett Healthcare, Cooperstown, NY 13326-1394, USA.
Ann Pharmacother. 2002 Mar;36(3):452-64. doi: 10.1345/aph.1A038.
To review the chemistry, spectrum of activity, pharmacology, clinical efficacy, and safety of telithromycin.
A MEDLINE search from 1966 to December 2000 was performed via OVID and PubMed using the following search terms: HMR 3647, HMR3647, Ketek, RU 66647, and telithromycin. An extensive review of retrieved literature, abstracts from international scientific conferences, and minutes from regulatory authority meetings was also performed.
Medicinal chemistry, in vitro, animal, and human trials were reviewed for information on the antimicrobial activity, clinical efficacy, pharmacology, and safety of telithromycin.
Several chemical modifications to the macrolide structure have led to the development of telithromycin, the first ketolide antimicrobial that demonstrates improved activity against penicillin- and macrolide/azalide-resistant Streptococcus pneumoniae due to its unique binding to the ribosomal target site. Although telithromycin may be useful in the treatment of community-acquired respiratory tract infections due to its activity against common typical and atypical pathogens, questions concerning its reliable activity against Haemophilus influenzae need to be addressed. Telithromycin's pharmacokinetics permit once-daily dosing for abbreviated periods and good distribution into lung tissue and phagocytic cells. Clinical and bacteriologic cure rates have been similar to those of comparator agents in human efficacy trials; however, the incidence of adverse gastrointestinal events were generally higher with telithromycin patients. Like other macrolides and many newer fluoroquinolones, telithromycin's ability to prolong the QTc interval is a potential safety issue, especially in elderly patients with predisposing conditions or those who are concurrently receiving drugs that are substrates for CYP2D6 and 3A4. Liver function test elevations demonstrated during clinical trials, although not overtly severe, may warrant monitoring in some patients taking multiple hepatically metabolized/cleared agents.
Telithromycin offers potential advantages over traditional macrolides/azalides for community-acquired respiratory tract infections caused by macrolide-resistant pathogens. Further studies are needed to elucidate its clinical efficacy against H. influenzae, potential drug interactions, and safety in various subpopulations.
综述泰利霉素的化学性质、活性谱、药理学、临床疗效及安全性。
通过OVID和PubMed对1966年至2000年12月期间的MEDLINE进行检索，检索词如下：HMR 3647、HMR3647、Ketek、RU 66647和泰利霉素。还对检索到的文献、国际科学会议摘要以及监管机构会议记录进行了广泛综述。
对药物化学、体外、动物及人体试验进行综述，以获取有关泰利霉素抗菌活性、临床疗效、药理学及安全性的信息。
对大环内酯结构进行的若干化学修饰导致了泰利霉素的研发，它是首个酮内酯类抗菌药物，由于其与核糖体靶位点的独特结合，对青霉素和大环内酯/氮杂内酯耐药的肺炎链球菌显示出增强的活性。尽管泰利霉素因其对常见典型和非典型病原体的活性可能对社区获得性呼吸道感染的治疗有用，但关于其对流感嗜血杆菌的可靠活性问题仍需解决。泰利霉素的药代动力学允许在较短疗程内每日给药一次，且在肺组织和吞噬细胞中分布良好。在人体疗效试验中，临床和细菌学治愈率与对照药物相似；然而，泰利霉素治疗的患者胃肠道不良事件发生率通常更高。与其他大环内酯类药物及许多新型氟喹诺酮类药物一样，泰利霉素延长QTc间期的能力是一个潜在的安全问题，尤其是在有易感因素的老年患者或同时接受CYP2D6和3A4底物药物的患者中。临床试验期间出现的肝功能检查升高，虽然并非明显严重，但在一些服用多种经肝脏代谢/清除药物的患者中可能需要进行监测。
对于由大环内酯耐药病原体引起的社区获得性呼吸道感染，泰利霉素相对于传统大环内酯类/氮杂内酯类药物具有潜在优势。需要进一步研究以阐明其对流感嗜血杆菌的临床疗效、潜在药物相互作用以及在不同亚组中的安全性。
