Van Wart Scott A, Andes David R, Ambrose Paul G, Bhavnani Sujata M
Institute for Clinical Pharmacodynamics, Ordway Research Institute, Latham, NY 12110, USA.
Diagn Microbiol Infect Dis. 2009 Apr;63(4):409-14. doi: 10.1016/j.diagmicrobio.2009.01.027. Epub 2009 Feb 26.
Dose regimen selection in late-phase clinical trials is critical for successful drug development, the well-being of individual patients, and given the ongoing emergence of antimicrobial resistance, society as a whole. Herein we describe some of the animal pharmacokinetics-pharmacodynamics, human pharmacokinetic, and in silico modeling work that was conducted in an effort to maximize the probability of a positive clinical response to therapy and minimize the likelihood for exposure-related toxicity for doripenem in phase 3 clinical studies. Some of the dosing regimens identified have been validated as effective in phase 3 clinical studies (500 mg infused over 1 h every 8 h for complicated intra-abdominal infections), whereas others (1000 mg infused over 4 h every 8 h for hospital-acquired pneumonia) are undergoing clinical evaluation.
在晚期临床试验中选择给药方案对于药物研发的成功、个体患者的健康状况以及鉴于抗菌药物耐药性的不断出现，对于整个社会而言都至关重要。在此，我们描述了一些动物药代动力学-药效学、人体药代动力学以及计算机模拟建模工作，这些工作旨在最大程度提高多利培南在3期临床研究中对治疗产生阳性临床反应的概率，并最小化与暴露相关毒性的可能性。所确定的一些给药方案已在3期临床研究中被验证为有效（用于复杂性腹腔内感染，每8小时1次，500 mg静脉输注1小时），而其他方案（用于医院获得性肺炎，每8小时1次，1000 mg静脉输注4小时）正在进行临床评估。
