Peking University Third Hospital, Beijing, China.
Peking University Third Hospital, Beijing, China
Antimicrob Agents Chemother. 2021 Feb 17;65(3). doi: 10.1128/AAC.01391-20.
Relebactam/imipenem/cilastatin is approved in the United States to treat complicated urinary tract and intra-abdominal infections in patients who have limited or no alternative treatment options and hospital-acquired bacterial pneumonia (HABP)/ventilator-associated bacterial pneumonia (VABP). Initial pharmacokinetic, safety, and tolerability studies of relebactam with and without imipenem/cilastatin included mostly Caucasian participants. This study evaluated the pharmacokinetics, safety, and tolerability of relebactam/imipenem/cilastatin in 12 healthy Chinese participants after three single doses of increasing concentrations (relebactam at 125, 250, or 500 mg; cilastatin at 250, 500, or 1,000 mg; and imipenem at 250, 500, or 1,000 mg) and after multiple doses every 6 h of a single concentration (relebactam at 250 mg, cilastatin at 500 mg, and imipenem at 500 mg) for 14 days. After single doses, the area under the concentration-time curve (AUC) extrapolated to infinity (relebactam, 15.0 to 70.7 h · mg/liter; imipenem, 24.1 to 109.8 h · mg/liter; cilastatin, 18.4 to 95.3 h · mg/liter) and the AUC from 0 to 6 h (relebactam, 14.2 to 66.3 h · mg/liter; imipenem, 23.4 to 107.3 h · mg/liter; cilastatin, 18.3 to 94.4 h · mg/liter) increased in a dose-dependent manner; clearance (relebactam, 6.9 to 8.3 liters/h; imipenem, 8.6 to 10.4 liters/h; cilastatin, 10.5 to 13.6 liters/h) and half-life (relebactam, 1.4 to 1.6 h; imipenem, 1.0 to 1.2 h; cilastatin, 0.7 to 1.0 h) were consistent between doses. Pharmacokinetic parameters after multiple doses were similar to parameters after a single dose (geometric mean ratios of 0.8 to 1.0 for all three agents). Relebactam/imipenem/cilastatin was well tolerated; mild adverse events occurred during single dosing, and one participant experienced serious adverse events after multiple doses. Pharmacokinetics and safety data are comparable with data from participants of other ethnicities, supporting the use of relebactam/imipenem/cilastatin at the approved dose and schedule in Chinese patients.
雷巴他定/亚胺培南/西司他丁在美国获批用于治疗有有限或无其他治疗选择的复杂性尿路感染和腹腔内感染，以及医院获得性细菌性肺炎（HABP）/呼吸机相关性细菌性肺炎（VABP）。雷巴他定联合或不联合亚胺培南/西司他丁的初步药代动力学、安全性和耐受性研究主要纳入了白种人参与者。本研究评估了 12 名健康中国参与者在接受递增浓度（雷巴他定 125、250 或 500mg；西司他丁 250、500 或 1000mg；亚胺培南 250、500 或 1000mg）的 3 次单剂量以及接受单剂量后每日每 6 小时给予 1 次、单剂量为 250mg 雷巴他定、500mg 西司他丁和 500mg 亚胺培南的 14 天多次剂量后，雷巴他定/亚胺培南/西司他丁的药代动力学、安全性和耐受性。单次给药后，药时曲线下面积（AUC）外推至无穷大（雷巴他定，15.0 至 70.7 小时·mg/L；亚胺培南，24.1 至 109.8 小时·mg/L；西司他丁，18.4 至 95.3 小时·mg/L）和 0 至 6 小时 AUC（雷巴他定，14.2 至 66.3 小时·mg/L；亚胺培南，23.4 至 107.3 小时·mg/L；西司他丁，18.3 至 94.4 小时·mg/L）呈剂量依赖性增加；清除率（雷巴他定，6.9 至 8.3L/h；亚胺培南，8.6 至 10.4L/h；西司他丁，10.5 至 13.6L/h）和半衰期（雷巴他定，1.4 至 1.6 小时；亚胺培南，1.0 至 1.2 小时；西司他丁，0.7 至 1.0 小时）在各剂量间一致。多次给药后的药代动力学参数与单次给药后的参数相似（所有三种药物的几何均数比值为 0.8 至 1.0）。雷巴他定/亚胺培南/西司他丁耐受性良好；单次给药时发生轻度不良事件，1 名参与者在多次给药后发生严重不良事件。药代动力学和安全性数据与其他种族参与者的数据相似，支持在中国患者中以批准的剂量和方案使用雷巴他定/亚胺培南/西司他丁。
