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BO-2727是由日本东京Banyu制药公司开发的注射用1-β-甲基碳青霉烯抗生素.化学名:(1R,5S,6S)-6-[(R)-1-羟乙基]-2-[(3S,5S)-5-[(R)-l-羟基-3-N-甲基-氨丙基]吡啶烷-3-基-硫]-1-甲基1碳青霉-2-烯-3-羧酸盐酸盐水合物(图1).BO-2727对革兰阳性菌和包括绿脓杆菌在内革兰阴性菌具有强大抗菌活性.实验动物毒性研究显示,它与已用于临床的亚胺培南/西司他丁钠一样安全.BO-2727对人肾脱氢肽酶(DHP-I)稳定,不需要合用像西司他丁钠那样的DHP-I酶抑制剂.BO-2727在恒河猴和黑猩猩中显示优越药代动力学性质,即它的AUC和血浆清除半衰期(T_1/2β)比亚胺培南/西司他丁或meropenem的大和长.鉴于临床前试验所验证中的BO-2727临床有效性,Nakashima在健康志愿者中进行了评价单剂量和多剂量下的耐受性和药代动力学研究.
BO-2727 is a 1-β-methylcarbapenem antibiotic for injection developed by Banyu Pharmaceutical Co., Ltd. in Tokyo, Japan Chemical name: (1R, 5S, 6S) -6 - [(R) -1-hydroxyethyl] -2 - [(3S, 5S) -5 - [(R) -l -hydroxy-3-N-methyl-aminopropyl] 2-ene-3-carboxylic acid hydrochloride hydrate (Figure 1) .BO-2727 has a potent antibacterial activity against Gram-positive bacteria and Pseudomonas aeruginosa including gram-negative bacteria.Experimental animal toxicity studies have shown that it Is as safe as clinically used imipenem / cilastatin sodium. BO-2727 is stable against human dehydropeptidase (DHP-I) and does not require the combination of DHP-I like cilastatin sodium Enzyme inhibitors.BO-2727 shows superior pharmacokinetic properties in rhesus and chimpanzees, ie its AUC and plasma clearance half-life (T_1 / 2β) are greater than those of imipenem / cilastatin or meropenem In view of the clinical validity of BO-2727 in preclinical trials, Nakashima was evaluated in healthy volunteers for single-dose and multiple-dose tolerance and pharmacokinetic studies.