Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
Covance Inc, Madison, WI, USA.
Clin Drug Investig. 2021 Jul;41(7):647-652. doi: 10.1007/s40261-021-01051-4. Epub 2021 Jun 7.
Omecamtiv mecarbil (OM) is a novel cardiac myosin activator in development for the treatment of heart failure with reduced ejection fraction. The objective of this study was to evaluate the potential for OM to affect the pharmacokinetics of metformin.
This was an open-label, fixed-sequence study in 14 healthy subjects. On Day 1, subjects received an 850 mg oral dose of metformin. From Days 4 to 9, subjects received twice-daily 25 mg oral doses of OM tablets. On Day 10, subjects received an 850 mg oral dose of metformin and a single 25 mg tablet of OM. Blood and urine samples were collected up to 36 h post-dose following administration of metformin on Days 1 and 10 to characterize concentrations of metformin in plasma and urine.
The ratios of the geometric least square means of metformin coadministered with OM compared to metformin alone were 98.7%, 99.3%, and 110.2% for AUC, AUC, and C, respectively. The mean renal clearance of metformin was similar following metformin administered alone (34.2 L/h) compared to metformin coadministered with OM (32.9 L/h). All adverse events were mild in severity and resolved prior to the end of the study. No serious adverse events or treatment-emergent adverse events led to discontinuation from the study.
There was no clinically relevant effect of OM on the pharmacokinetics of metformin in healthy subjects.
Omecamtiv mecarbil（OM）是一种新型心肌肌球蛋白激活剂，正在开发用于治疗射血分数降低的心力衰竭。本研究的目的是评估 OM 对二甲双胍药代动力学的潜在影响。
这是一项在 14 名健康受试者中进行的开放标签、固定序列研究。第 1 天，受试者接受 850 mg 口服剂量的二甲双胍。第 4 天至第 9 天，受试者每天口服两次 25 mg OM 片剂。第 10 天，受试者接受 850 mg 口服剂量的二甲双胍和 1 片 25 mg OM。在第 1 天和第 10 天给予二甲双胍后，采集 36 小时内的血样和尿样，以确定血浆和尿液中二甲双胍的浓度。
与单独给予二甲双胍相比，与 OM 联合给予的二甲双胍的几何最小二乘均值比值分别为 AUC、AUC 和 C 的 98.7%、99.3%和 110.2%。单独给予二甲双胍时的平均肾清除率（34.2 L/h）与与 OM 联合给予时相似（32.9 L/h）。所有不良事件均为轻度，在研究结束前已解决。无严重不良事件或治疗中出现的不良事件导致研究中止。
在健康受试者中，OM 对二甲双胍的药代动力学无临床相关影响。
