School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, New York, USA..
Clin Infect Dis. 2011 Jun;52 Suppl 7:S513-9. doi: 10.1093/cid/cir166.
Perhaps the most crucial step in the clinical development of an antimicrobial agent is the selection of a dosing regimen. Such decisions impact not only the success of a program but also the well being of individual patients, the emergence of resistance, and society as a whole. For fusidic acid, the selection of a dosing regimen for the treatment of patients with acute bacterial skin and skin-structure infection (ABSSSI) was based on the integration of knowledge gained from human population pharmacokinetic, in vitro infection, and mathematical models. The overarching goal of these studies was to identify a dosing regimen that would maximize the probabilities of positive clinical outcomes and limit the emergence of bacterial resistance during therapy. Novel dosing regimens identified included 1500 mg twice daily on day 1 followed by 600 mg twice daily for 10-14 days, a regimen that was subsequently found to be effective in a phase 2 clinical study of patients with ABSSSI. Herein, we review the data supporting the use of this novel fusidic acid dosing regimen, which will undergo further clinical evaluation in phase 3 clinical trials.
也许抗菌药物临床开发中最重要的步骤是选择给药方案。这些决策不仅影响到一个项目的成败，还影响到个体患者的健康、耐药性的出现以及整个社会。对于夫西地酸，治疗急性细菌性皮肤和皮肤结构感染（ABSSSI）患者的给药方案选择是基于从人体群体药代动力学、体外感染和数学模型中获得的知识的整合。这些研究的总体目标是确定一种给药方案，最大限度地提高阳性临床结果的概率，并在治疗过程中限制细菌耐药性的出现。确定的新给药方案包括第 1 天每天两次 1500mg，然后每天两次 600mg 持续 10-14 天，随后在 ABSSSI 患者的 2 期临床研究中发现该方案有效。本文综述了支持使用这种新型夫西地酸给药方案的研究数据，该方案将在 3 期临床试验中进行进一步的临床评估。
