Odenholt Inga, Cars Otto, Löwdin Elisabeth
Antibiotic Research Unit, Department of Medical Sciences, Infectious Diseases and Clinical Bacteriology, Uppsala University, 20502 Malmö, Sweden.
J Antimicrob Chemother. 2004 Dec;54(6):1062-6. doi: 10.1093/jac/dkh484. Epub 2004 Nov 24.
To compare the pharmacodynamic effects of a pharmacokinetically enhanced formulation of amoxicillin 2000 mg twice daily, with amoxicillin 875 mg twice daily, 875 mg three times daily and 500 mg three times daily against Streptococcus pneumoniae with different susceptibility to amoxicillin in an in vitro kinetic model.
Strains of S. pneumoniae with amoxicillin MICs of 1, 2, 4 and 8 mg/L at an initial inoculum of approximately 10(5) cfu/mL were exposed to amoxicillin in an in vitro kinetic model simulating the human serum concentration-time profile of the pharmacokinetically enhanced formulation twice daily (C(max) 17 mg/L after 1.5 h). All isolates were also exposed to amoxicillin with concentration-time profiles correlating to the human dosage of 875 mg twice daily (C(max) 15 mg/L after 1 h), 875 mg three times daily and 500 mg (C(max) 8 mg/L after 1 h) three times daily with simulated half-life of 1 h. Repeated samples were taken regularly during 24 h and viable counts were carried out.
Overall, the pharmacokinetically enhanced formulation was more effective at reducing bacterial counts than any of the other formulations evaluated. Eradication was achieved with the enhanced formulation for strains with a MIC of < or =2 mg/L, however, regrowth occurred with the other dosing regimens. In the experiments with the strain with a MIC of 4 mg/L, the enhanced formulation kept the bacterial counts < or =10(2) cfu/mL for at least 14 out of 24 h tested. In contrast, none of the other formulations reduced the bacterial counts down to < or =10(2) cfu/mL at any point. None of the regimens was able to eradicate the strain with an MIC of 8 mg/L, even though an initial substantial kill was noted with the enhanced formulation after both doses. The least effective dosage regimen for all strains was 875 mg twice daily.
在体外动力学模型中，比较每日两次服用2000毫克药代动力学增强型阿莫西林制剂与每日两次服用875毫克阿莫西林、每日三次服用875毫克阿莫西林以及每日三次服用500毫克阿莫西林对不同阿莫西林敏感性的肺炎链球菌的药效学作用。
在体外动力学模型中，将初始接种量约为10(5) cfu/mL、阿莫西林最低抑菌浓度（MIC）分别为1、2、4和8毫克/升的肺炎链球菌菌株暴露于模拟药代动力学增强型制剂每日两次人体血清浓度-时间曲线的阿莫西林中（1.5小时后C(max)为17毫克/升）。所有分离株还暴露于浓度-时间曲线与每日两次服用875毫克（1小时后C(max)为15毫克/升）、每日三次服用875毫克以及每日三次服用500毫克（1小时后C(max)为8毫克/升）人体剂量相关且模拟半衰期为1小时的阿莫西林中。在24小时内定期采集重复样本并进行活菌计数。
总体而言，药代动力学增强型制剂在降低细菌数量方面比所评估的任何其他制剂都更有效。对于MIC≤2毫克/升的菌株，增强型制剂实现了根除，然而，其他给药方案出现了细菌再生长。在MIC为4毫克/升菌株的实验中，增强型制剂在测试的24小时内至少14小时使细菌数量≤10(2) cfu/mL。相比之下，其他制剂在任何时间点都未将细菌数量降低至≤10(2) cfu/mL。即使在两次给药后增强型制剂最初有大量杀菌作用，也没有一种给药方案能够根除MIC为8毫克/升的菌株。对所有菌株最无效的给药方案是每日两次服用875毫克。
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