Bayer AG, Research & Development, Pharmaceuticals, Translational Medicine, 42096, Wuppertal, Germany.
Bayer AG, Research & Development, Pharmaceuticals, Pharmacometrics, Leverkusen, Germany.
Clin Pharmacokinet. 2023 Dec;62(12):1673-1693. doi: 10.1007/s40262-023-01312-9. Epub 2023 Oct 24.
Finerenone, a selective and nonsteroidal antagonist of the mineralocorticoid receptor, has received regulatory approval with the indication of cardiorenal protection in patients with chronic kidney disease associated with type 2 diabetes. It is rapidly and completely absorbed and undergoes first-pass metabolism in the gut wall and liver resulting in a bioavailability of 43.5%. Finerenone can be taken with or without food. The pharmacokinetics of finerenone are linear and its half-life is 2 to 3 h in the dose range of up to 20 mg. Cytochrome P450 (CYP) 3A4 (90%) and CYP2C8 (10%) are involved in the extensive biotransformation of finerenone to pharmacologically inactive metabolites, which are excreted via both renal (80%) and biliary (20%) routes. Moderate or severe renal impairment, or moderate hepatic impairment result in area-under-the-curve increases of finerenone (< 40%), which do not require a dose adjustment per se, as the starting dose is based on estimated glomerular filtration rate (eGFR) and titrated according to serum potassium levels and eGFR decline. No relevant effects of age, sex, body size or ethnicity on systemic finerenone exposure were identified. Modulators of CYP3A4 activity were found to affect finerenone exposure, consistent with its classification as a sensitive CYP3A4 substrate. Serum potassium should be monitored during drug initiation or dosage adjustment of either a moderate or weak CYP3A4 inhibitor or finerenone, and the dose of finerenone should be adjusted as appropriate. Its use with strong inhibitors is contraindicated and strong or moderate inducers of CYP3A4 should be avoided. Finerenone has no potential to affect relevant CYP enzymes and drug transporters.
非奈利酮是一种选择性、非甾体盐皮质激素受体拮抗剂，已获得批准用于治疗伴有 2 型糖尿病的慢性肾脏病患者的心脏肾脏保护。它在胃肠道和肝脏中迅速且完全被吸收，并经历首过代谢，导致其生物利用度为 43.5%。非奈利酮可在有或无食物的情况下服用。非奈利酮的药代动力学呈线性，在 0-20mg 剂量范围内其半衰期为 2-3 小时。细胞色素 P450（CYP）3A4（90%）和 CYP2C8（10%）广泛参与非奈利酮向无药理活性代谢物的生物转化，这些代谢物通过肾脏（80%）和胆汁（20%）途径排泄。中重度肾功能损害或中重度肝功能损害导致非奈利酮的曲线下面积（AUC）增加（<40%），但通常不需要调整剂量，因为起始剂量是基于估算的肾小球滤过率（eGFR），并根据血清钾水平和 eGFR 下降情况进行滴定。未发现年龄、性别、体型或种族对全身非奈利酮暴露有相关影响。CYP3A4 活性调节剂被发现会影响非奈利酮的暴露，这与其被分类为敏感 CYP3A4 底物一致。在开始使用或调整中度或弱 CYP3A4 抑制剂或非奈利酮的剂量时，应监测血清钾，并且应根据需要调整非奈利酮的剂量。禁止将其与强抑制剂联合使用，并且应避免使用强或中度 CYP3A4 诱导剂。非奈利酮不会影响相关 CYP 酶和药物转运体。
