Bayer AG, Research & Development, Pharmaceuticals, Translational Medicine, 42096, Wuppertal, Germany.
Chrestos Concept GmbH & Co. KG, Essen, Germany.
Eur J Drug Metab Pharmacokinet. 2022 Jul;47(4):549-559. doi: 10.1007/s13318-022-00770-z. Epub 2022 May 25.
Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that reduces the risk of adverse kidney and cardiovascular outcomes in patients with chronic kidney disease associated with type 2 diabetes mellitus. Clinical phase I studies with finerenone were carried out to assess its pharmacokinetics and the influence of common covariables on its absorption after oral administration.
Three crossover studies in healthy male volunteers with single-dose administration of finerenone investigated the dose linearity of a film-coated tablet (1.25-10 mg [n = 24] and 10-20 mg [n = 18]), the effect of food on the 20 mg tablet (n = 18), and the effects of the proton-pump inhibitor omeprazole (4 days pre-treatment and co-administration 2 h before finerenone) and an aluminum/magnesium hydroxide-containing antacid (10 mL [Maalox] 70 mVal, simultaneous intake) on the 10 mg tablet (n = 10 and n = 11, respectively).
Finerenone was rapidly absorbed (time to reach maximum plasma concentration [t] was 0.50-0.75 h). Area under the curve from zero to infinity (AUC) and the maximum concentration (C) increased in proportion to dose in the range investigated in clinical phase II and phase III studies (1.25-20 mg), with point estimates for the ratio of dose-normalized AUC and C (20 mg/10 mg, approved therapeutic doses) of 0.9943 and 0.9301. After the administration of finerenone 20 mg with a high-fat, high-calorie meal, AUC increased (+ 21%), C decreased (-19%), and t was prolonged (2.47 vs. 0.75 h) when compared with the fasting state. Omeprazole had no effect on finerenone AUC and C. Maalox had no effect on finerenone AUC and led to a non-clinically-relevant decrease in C (-19%).
The pharmacokinetics of the finerenone film-coated tablet were linear. High-fat, high-calorie food had no clinically relevant effect on the pharmacokinetics of finerenone. In addition, pH-modifying comedications were not found to alter the pharmacokinetics of finerenone and were deemed safe for co-administration.
非奈利酮是一种非甾体类盐皮质激素受体拮抗剂，可降低伴有 2 型糖尿病的慢性肾脏病患者的不良肾脏和心血管结局风险。非奈利酮的临床 I 期研究旨在评估其药代动力学，并研究常见伴随变量对其口服吸收的影响。
在健康男性志愿者中进行了 3 项单剂量给药的交叉研究，以评估薄膜包衣片剂（1.25-10 mg [n = 24] 和 10-20 mg [n = 18]）的剂量线性关系、食物对 20 mg 片剂的影响（n = 18）、质子泵抑制剂奥美拉唑（4 天预处理和 2 小时前共同给予非奈利酮）和含铝/镁氢氧化物的抗酸剂（10 mL [Maalox] 70 mVal，同时摄入）对 10 mg 片剂的影响（n = 10 和 n = 11）。
非奈利酮吸收迅速（达峰时间 [t] 为 0.50-0.75 h）。在临床 II 期和 III 期研究（1.25-20 mg）中，AUC 和 C 从 0 到无穷大的面积（AUC）与剂量呈比例增加，剂量归一化 AUC 和 C 的比值（20 mg/10 mg，批准的治疗剂量）的点估计值为 0.9943 和 0.9301。与空腹状态相比，高脂肪、高热量饮食给予非奈利酮 20 mg 后，AUC 增加（+21%），C 降低（-19%），t 延长（2.47 比 0.75 h）。奥美拉唑对非奈利酮 AUC 和 C 无影响。Maalox 对非奈利酮 AUC 无影响，导致 C 非临床相关下降（-19%）。
非奈利酮薄膜包衣片剂的药代动力学呈线性。高脂肪、高热量饮食对非奈利酮的药代动力学无临床相关影响。此外，未发现 pH 调节伴随药物改变非奈利酮的药代动力学，且联合使用安全。
