Iwai N, Nakamura H, Taneda Y
Department of Pediatrics, Meitetsu Hospital.
Jpn J Antibiot. 1994 Dec;47(12):1706-22.
Pharmacokinetic, bacteriological and clinical studies on biapenem (L-627), a newly developed carbapenem antibiotic, were performed in the field of pediatrics. 1. Antibacterial activities of biapenem against 54 strains of Streptococcus pneumoniae isolated in 1993 were compared with those of 13 other antibiotics, consisting primarily of beta-lactam compounds. Minimal inhibitory concentrations (MICs) of biapenem were < or = 0.78 micrograms/ml against all strains, and excellent values were obtained even against benzylpenicillin (PCG)-resistant strains. Based on MIC80 values, biapenem, imipenem, and cefuzonam showed highest antibacterial activities, followed by cefotaxime. 2. Blood concentrations and urinary excretion were studied after intravenous drip infusion of 6.0 mg/kg and 6.1 mg/kg of biapenem, given over 30 min., to two children (ages: 4 years and 11 years). Blood drug concentrations were 14.7 and 37.6 micrograms/ml, respectively (mean: 26.2 micrograms/ml), at 30 min. after starting infusion (at completion of infusion). Blood concentrations then declined gradually with half-lives of 0.66 and 1.16 hrs., respectively (mean: 0.91 hrs.). After 5.5 hrs., blood concentrations were no longer measurable in the former and 0.46 micrograms/ml in the latter. Urinary recovery rates of drug in the first 6 hrs. after starting administration were 65.8% and 60.9%, respectively (mean 63.4%). 3. Penetration of the drug to the cerebrospinal fluid (CSF) was studied in 2 patients with purulent meningitis. Biapenem, 31.6 mg/kg, was administered four times daily by 30-min. intravenous drip infusion. CSF concentration 1 hr. after administration was 8.54 micrograms/ml on the day of the start of treatment (day 0), and 3.00, 2.04, 16.1, 4.16, 3.24, and 1.60 micrograms/ml on days 1-7 of treatment, respectively. In a patient similarly administered with the drug at 33.7 mg/kg four times daily, the CSF concentration at 1.5 hrs. after administration was 2.62 micrograms/ml on the next day of the start of treatment. On days 2-7 of treatment, CSF concentrations at 0.5-1 hr. after administration were 4.60, 12.9, 20.6, and 1.32 micrograms/ml, respectively. 4. Clinical efficacy was evaluated in 27 patients with pediatric infections. The dose administered per dosage was 5.2-33.7 mg/kg. Three or four dosages were given daily. The duration of therapy ranged from 3 1/3 to 11 days. Total administered doses were between 0.675 and 20.475 g. Clinical efficacy was evaluated in a total of 24 patients (purulent meningitis 1, acute otitis media 1, acute bronchitis 2, acute pneumonia 19, acute urinary tract infection 1). Responses to treatment were excellent in 14 patients and good in 10 patients.(ABSTRACT TRUNCATED AT 400 WORDS)
对新开发的碳青霉烯类抗生素比阿培南（L - 627）进行了儿科领域的药代动力学、细菌学及临床研究。1. 将比阿培南对1993年分离出的54株肺炎链球菌的抗菌活性与其他13种主要为β - 内酰胺类化合物的抗生素进行了比较。比阿培南对所有菌株的最低抑菌浓度（MICs）均≤0.78微克/毫升，即使对耐苄青霉素（PCG）菌株也取得了优异的值。基于MIC80值，比阿培南、亚胺培南和头孢唑南显示出最高的抗菌活性，其次是头孢噻肟。2. 对两名儿童（年龄分别为4岁和11岁）静脉滴注6.0毫克/千克和6.1毫克/千克比阿培南（30分钟内滴完）后，研究了血药浓度和尿排泄情况。开始输注后30分钟（输注结束时）血药浓度分别为14.7和37.6微克/毫升（平均：26.2微克/毫升）。随后血药浓度逐渐下降，半衰期分别为0.66和1.16小时（平均：0.91小时）。5.5小时后，前者血药浓度无法测出，后者为0.46微克/毫升。给药后前6小时药物的尿回收率分别为65.8%和60.9%（平均63.4%）。3. 对2例化脓性脑膜炎患者研究了药物在脑脊液（CSF）中的渗透情况。比阿培南31.6毫克/千克，每日4次，30分钟静脉滴注。治疗开始当天（第0天）给药后1小时脑脊液浓度为8.54微克/毫升，治疗第1 - 7天分别为3.00、2.04、16.1、4.16、3.24和1.60微克/毫升。在一名同样每日4次给予33.7毫克/千克该药物的患者中，给药后1.5小时脑脊液浓度在治疗开始后次日为2.62微克/毫升。在治疗第2 - 7天，给药后0.5 - 1小时脑脊液浓度分别为4.60、12.9、20.6和1.32微克/毫升。4. 对27例儿科感染患者评估了临床疗效。每次给药剂量为5.2 - 33.7毫克/千克。每日给药3或4次。治疗持续时间为3又1/3至11天。总给药剂量在0.675至20.475克之间。共对24例患者（化脓性脑膜炎1例、急性中耳炎1例、急性支气管炎2例、急性肺炎19例、急性尿路感染1例）评估了临床疗效。14例患者治疗反应为优，10例为良。（摘要截于400字）
