Hirabayashi K, Okada E
Jpn J Antibiot. 1986 May;39(5):1413-25.
Fundamental and clinical studies of imipenem (MK-0787), a new type of carbapenem antibiotic, and MK-0787 combined with cilastatin sodium (MK-0791), a renal dipeptidase inhibitor, were carried out. The results obtained were as follows: MK-0787 500 mg alone or MK-0787 500 mg with MK-0791 500 mg was administered by intravenous drip infusion over 30 minutes. Plasma levels of the drug were similar either following the administration of 500 mg of MK-0787 alone or 500 mg of MK-0787 with 500 mg of MK-0791. When MK-0787 was administered with MK-0791, MK-0787 and MK-0791 levels at 2 hours after the end of infusion in uterine arterial plasma were 6.8 micrograms/ml and 3.2 micrograms/ml, respectively, and in venous plasma were 8.4 micrograms/ml and 4.7 micrograms/ml, respectively. MK-0787 tissue levels ranged from 0.8 microgram/g to 3.8 micrograms/g at 205 minutes after the end of infusion. Based on these results, the plasma and tissue levels of MK-0787 and MK-0791 with b.i.d. dosage exceeded the MICs of the drug against clinical isolates in the field of obstetrics and gynecology such as E. faecalis, E. coli Klebsiella sp., Peptococcus sp., Peptostreptococcus sp. and B. fragilis immediately after the administration. However, it seemed that the b.i.d. dosage was insufficient to maintain the in vivo concentration of these agents high enough to inhibit the growth of the above bacteria. Eighteen patients with obstetric and gynecologic infection (12 with intrauterine infections, 2 with pelvic dead space inflammation, 2 with pelvic peritonitis, 1 with a vaginal cuff abscess and 1 with a vulvar abscess) and 1 patient with other infection (abdominal wall abscess) were evaluated, but 1 patient with pelvic peritonitis was later excluded from the efficacy evaluation because of a serious illness. MK-0787/MK-0791 was administered twice daily in a 30-minute intravenous drip infusion. Clinical results were excellent in 1 patient, good in 16 and poor in 1, for an efficacy ratio of 94.4%. No side effects were observed. Only abnormal laboratory findings observed were elevation of S-GOT and S-GPT in 1 patient which normalized 2 weeks after the treatment was discontinued. These results suggest that MK-0787/MK-0791 will be useful for the treatment of obstetric and gynecologic infections.
对新型碳青霉烯类抗生素亚胺培南（MK - 0787）以及亚胺培南与肾二肽酶抑制剂西司他丁钠联合制剂（MK - 0791）进行了基础和临床研究。获得的结果如下：单独静脉滴注30分钟给予500mg MK - 0787，或给予500mg MK - 0787与500mg MK - 0791。单独给予500mg MK - 0787或给予500mg MK - 0787与500mg MK - 0791后，药物的血浆水平相似。当MK - 0787与MK - 0791联合使用时，输注结束后2小时子宫动脉血浆中MK - 0787和MK - 0791的水平分别为6.8微克/毫升和3.2微克/毫升，静脉血浆中分别为8.4微克/毫升和4.7微克/毫升。输注结束后205分钟，MK - 0787的组织水平在0.8微克/克至3.8微克/克之间。基于这些结果，每日两次给药时，MK - 0787和MK - 0791的血浆和组织水平在给药后立即超过了该药物对妇产科临床分离株如粪肠球菌、大肠杆菌、克雷伯菌属、消化球菌属、消化链球菌属和脆弱拟杆菌的最低抑菌浓度。然而，每日两次给药似乎不足以使这些药物在体内维持足够高的浓度以抑制上述细菌的生长。对18例妇产科感染患者（12例为宫内感染，2例为盆腔死腔炎症，2例为盆腔腹膜炎，1例为阴道残端脓肿，1例为外阴脓肿）和1例其他感染患者（腹壁脓肿）进行了评估，但1例盆腔腹膜炎患者因病情严重后来被排除在疗效评估之外。MK - 0787/MK - 0791每日静脉滴注30分钟给药两次。临床结果为1例优，16例良，1例差，有效率为94.4%。未观察到副作用。仅1例患者观察到实验室检查异常结果为谷草转氨酶和谷丙转氨酶升高，停药2周后恢复正常。这些结果表明MK - 0787/MK - 0791对治疗妇产科感染将是有用的。
