Nishimura T, Tabuki K, Takashima T, Takagi M
Jpn J Antibiot. 1985 Feb;38(2):431-40.
The authors have carried out laboratory and clinical studies on the BRL 25000 granule (containing 2 parts amoxicillin and 1 part clavulanic acid). The antibacterial activity of BRL 25000 against 29 clinically isolated strains of S. aureus, 30 E. coli and 30 K. pneumoniae were measured by the agar dilution method using an inoculum size of 10(6) cells/ml. beta-Lactamase production was detected by the Nitrocefin method. The MICs of BRL 25000 against S. aureus ranged from 0.2 approximately 12.5 micrograms/ml, with the majority of strains being inhibited by 1.56 micrograms/ml or less. Seven beta-lactamase producing strains of S. aureus were all inhibited by less than 12.5 micrograms/ml. The range against E. coli was 1.56 approximately 100 micrograms/ml, with the majority inhibited by 6.25 micrograms/ml or less. Fifteen beta-lactamase producing strains of E. coli were inhibited by 6.25 approximately 100 micrograms/ml and the majority by 25 micrograms/ml or less. All strains of K. pneumoniae were beta-lactamase producers and the MIC distribution against K. pneumoniae was 1.56 approximately 50 micrograms/ml, with a majority inhibited by 3.13 micrograms/ml or less, 96% of strains, were inhibited by less than 6.25 micrograms/ml. Against K. pneumoniae, BRL 25000 showed a 8 to 16-fold superiority when compared with AMPC. In a pharmacokinetic study, BRL 25000 granules were orally administered to children in the fasting state at single doses of 7.5 mg/kg and 20 mg/kg. The peak serum levels of AMPC were 6.13 and 6.94 micrograms/ml approximately 1 hour after administration and decreased with half-lives of 1.08 and 0.97 hours, respectively. The corresponding serum levels of CVA were 1.16 and 1.90 micrograms/ml at 1 hour after administration, with half-lives of 0.99 and 0.87 hour, respectively. In clinical studies, the BRL 25000 granule was effective in 39 cases of bacterial infection out of a total of 41 treated. Side effects were limited to 2 cases of diarrhea and minor changes in laboratory findings were elevation of serum GOT (1 case), elevation of serum GPT (1 case), and eosinophilia (2 cases).
作者对BRL 25000颗粒（含2份阿莫西林和1份克拉维酸）进行了实验室和临床研究。采用琼脂稀释法，接种量为10⁶个细胞/ml，测定了BRL 25000对29株临床分离的金黄色葡萄球菌、30株大肠杆菌和30株肺炎克雷伯菌的抗菌活性。采用头孢硝噻吩试验检测β-内酰胺酶的产生。BRL 25000对金黄色葡萄球菌的MIC范围为0.2～12.5μg/ml，大多数菌株被1.56μg/ml或更低浓度所抑制。7株产β-内酰胺酶的金黄色葡萄球菌菌株均被低于12.5μg/ml的浓度所抑制。对大肠杆菌的MIC范围为1.56～100μg/ml，大多数菌株被6.25μg/ml或更低浓度所抑制。15株产β-内酰胺酶的大肠杆菌菌株被6.25～100μg/ml的浓度所抑制，大多数被25μg/ml或更低浓度所抑制。所有肺炎克雷伯菌菌株均产β-内酰胺酶，BRL 25000对肺炎克雷伯菌的MIC分布为1.56～50μg/ml，大多数菌株被3.13μg/ml或更低浓度所抑制，96%的菌株被低于6.25μg/ml的浓度所抑制。与氨曲南相比，BRL 25000对肺炎克雷伯菌显示出8至16倍的优势。在一项药代动力学研究中，对空腹状态的儿童口服单剂量7.5mg/kg和20mg/kg的BRL 25000颗粒。给药后约1小时，阿莫西林的血清峰值水平分别为6.13和6.94μg/ml，半衰期分别为1.08和0.97小时。给药后1小时，克拉维酸的相应血清水平分别为1.16和1.90μg/ml，半衰期分别为0.99和0.87小时。在临床研究中，41例接受治疗的细菌感染患者中，BRL 25000颗粒对39例有效。副作用仅限于2例腹泻，实验室检查的轻微变化为血清谷草转氨酶升高（1例）、血清谷丙转氨酶升高（1例）和嗜酸性粒细胞增多（2例）。
