Ishihara Noriyuki, Nishimura Nobuhiro, Tamaki Hiroki, Karino Fumi, Miura Kiyotaka, Isobe Takeshi, Ikawa Kazuro, Morikawa Norifumi, Naora Kohji
Int J Clin Pharmacol Ther. 2015 Jun;53(6):422-9. doi: 10.5414/CP202191.
Meropenem (MEPM) and doripenem (DRPM), whose antipseudomonal activity is more potent than that of other carbapenem antimicrobials, were used in the study. Monte Carlo simulation of drug concentrations was performed to develop an administration plan for MEPM and DRPM that takes into account the pharmacokinetics (PK)-pharmacodynamics (PD) of MEPM and DRPM and the renal function of each patient. Drug administration plans were proactively applied to patients with pneumonia to determine the usefulness of the method by assessing treatment efficacy and safety.
Patients with healthcareassociated pneumonia and an indication for MEPM or DRPM chemotherapy underwent drug administration in accordance with the MEPM and DRPM treatment plan developed by the PK-PD software applications. The primary efficacy endpoints were the clinical and bacteriological efficacy of the drugs agains pneumonia. The safety of the antimicrobials was assessed based on abnormal laboratory findings and the seizure disorders in accordance with the criteria for safety evaluation of antimicrobial agents.
This study examined 12 and 11 patients in the MEPM and DRPM group, respectively; however, 3 DRPM patients were excluded due to the administration of anti-methicillin-resistant Staphylococcus aureus drugs after the initiation of DRPM treatment. MEPM and DRPM drug administration was determined to be safe and effective in all patients.
The present results suggest that the Monte Carlo simulation-based PK-PD software is an effective tool for planning individualized antimicrobial chemotherapy with carbapenem in accordance with the PK-PD theory of antimicrobials. It is also possible to propose safe and effective drug administration plans for patients with healthcare-associated pneumonia.
本研究使用了美罗培南（MEPM）和多利培南（DRPM），其抗假单胞菌活性比其他碳青霉烯类抗菌药物更强。进行了药物浓度的蒙特卡洛模拟，以制定美罗培南和多利培南的给药方案，该方案考虑了美罗培南和多利培南的药代动力学（PK）-药效学（PD）以及每位患者的肾功能。将给药方案积极应用于肺炎患者，通过评估治疗效果和安全性来确定该方法的实用性。
患有医疗相关肺炎且有美罗培南或多利培南化疗指征的患者，按照PK-PD软件应用程序制定的美罗培南和多利培南治疗方案进行给药。主要疗效终点是药物对肺炎的临床和细菌学疗效。根据抗菌药物安全性评价标准，基于实验室检查异常和癫痫发作情况评估抗菌药物的安全性。
本研究分别对美罗培南组和多利培南组的12例和11例患者进行了检查；然而，3例多利培南患者在多利培南治疗开始后因使用抗耐甲氧西林金黄色葡萄球菌药物而被排除。确定美罗培南和多利培南给药对所有患者均安全有效。
目前的结果表明，基于蒙特卡洛模拟的PK-PD软件是一种有效的工具，可根据抗菌药物的PK-PD理论规划碳青霉烯类抗菌药物的个体化化疗。也有可能为医疗相关肺炎患者提出安全有效的给药方案。
