Clinical Pharmacology, Bayer AG, Research & Development, Building 0520, 42096, Wuppertal, Germany.
Experimental Medicine 1, Bayer AG, Wuppertal, Germany.
Clin Pharmacokinet. 2023 Feb;62(2):321-333. doi: 10.1007/s40262-022-01203-5. Epub 2023 Feb 2.
Vericiguat is approved for the treatment of patients with heart failure with ejection fraction < 45%. Sildenafil, indicated for the treatment of erectile dysfunction, is a potential co-medication in male patients. This study investigated the safety and tolerability of co-administration of vericiguat and sildenafil in healthy volunteers.
This was a single-center, randomized, placebo-controlled, parallel-group study in 32 healthy white male volunteers. Participants received vericiguat 10 mg or placebo once daily for 16 days. Both groups received single doses of sildenafil (25 mg, 50 mg, and 100 mg) on days 13-15. Safety, hemodynamic changes, and pharmacokinetic effects were assessed.
All subjects in the vericiguat group and seven (43.8%) in the placebo group reported one or more treatment-emergent adverse events, all of mild or moderate intensity. Decreases in seated blood pressure (≤ 5.4 mmHg) with the vericiguat-sildenafil combination compared with placebo-sildenafil were small and there was no evidence of a sildenafil dose-related effect. Standing blood pressure and standing and seated heart rate were similar between treatment groups. Co-administration of sildenafil did not affect vericiguat pharmacokinetics. A mild increase in sildenafil exposure (≤ 22%) when co-administered with vericiguat was observed.
Adding single doses of sildenafil to vericiguat 10 mg once daily at steady state was well tolerated and produced a minimal reduction in seated blood pressure (≤ 5.4 mmHg) compared with administration of sildenafil alone. There was no effect of sildenafil on vericiguat pharmacokinetics, and an increase in sildenafil exposure with vericiguat co-administration was not clinically relevant.
EudraCT no. 2015-004997-14.
维立西呱获批用于射血分数<45%的心衰患者的治疗。西地那非用于治疗勃起功能障碍，是男性患者的潜在合并用药。本研究旨在评估健康志愿者中维立西呱与西地那非合并用药的安全性和耐受性。
这是一项在 32 名健康白种男性志愿者中开展的、单中心、随机、安慰剂对照、平行分组研究。参与者接受维立西呱 10mg 或安慰剂，每日 1 次，连续用药 16 天。两组志愿者在第 13-15 天分别接受单次西地那非（25mg、50mg 和 100mg）给药。评估安全性、血流动力学变化和药代动力学效应。
维立西呱组所有受试者和安慰剂组 7 名（43.8%）受试者报告了 1 次或多次治疗期间出现的不良事件，均为轻度或中度。与安慰剂-西地那非组相比，维立西呱-西地那非组的坐位血压下降（≤5.4mmHg）较小，且无西地那非剂量相关性效应证据。两组的站立血压和站、坐位心率相似。西地那非不影响维立西呱的药代动力学。与单独使用维立西呱相比，合并使用时观察到西地那非暴露轻度增加（≤22%）。
在稳态下，每日给予维立西呱 10mg 同时单次给予西地那非，耐受性良好，与单独使用西地那非相比，坐位血压（≤5.4mmHg）仅出现轻微降低。西地那非对维立西呱的药代动力学无影响，与维立西呱合用时西地那非暴露增加无临床意义。
EudraCT 编号 2015-004997-14。
