Ishibashi Shun, Arai Hidenori, Yokote Koutaro, Araki Eiichi, Watanabe Mao, Nakanishi Michiko, Makinose Yuichi, Suganami Hideki, Kurihara Yuji, Yamashita Shizuya
Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, Jichi Medical University.
Ishibashi Diabetes and Endocrine Clinic.
J Atheroscler Thromb. 2025 Feb 1;32(2):210-225. doi: 10.5551/jat.64887. Epub 2024 Sep 5.
Per the package insert, pemafibrate was contraindicated for use in patients with severe renal impairment despite its biliary excretion. To validate this, we evaluated the pharmacokinetics and safety of pemafibrate for 12 weeks in patients with hypertriglyceridemia and renal impairment.
In this phase 4, multicenter, placebo-controlled, double-blind, parallel-group, comparative study, 21 patients were randomly assigned to pemafibrate 0.2 mg/day or placebo within Groups A (estimated glomerular filtration rate [eGFR] ＜30 mL/min/1.73m without hemodialysis; pemafibrate n=4; placebo, n=2), B (hemodialysis; pemafibrate, n=4; placebo, n=1), and C (eGFR ≥ 30 and ＜60 mL/min/1.73m without hemodialysis; pemafibrate, n=8; placebo, n=2) for 12 weeks. Area under the concentration vs time curve within the dosing interval (τ) (AUC) of pemafibrate was measured after 12-week administration.
The AUC (geometric mean) of pemafibrate was 7.333 and 7.991 ng·h/mL in Groups A+B and C, respectively; in Groups A+B to C at 12 weeks, the geometric mean ratio of pemafibrate AUC was 0.92 (90% confidence interval [CI]: 0.62, 1.36). The upper limit of the 90% CI was ≤ 2.0 (predetermined criterion). There was no consistent trend in the AUC and maximum plasma concentration of pemafibrate with/without statin use. Renal impairment degree did not affect the incidence of adverse events. No safety concerns were observed.
Pemafibrate repeated administration in patients with severe renal impairment did not increase pemafibrate exposure.
根据药品说明书，非诺贝特尽管经胆汁排泄，但仍禁用于重度肾功能不全患者。为验证这一点，我们评估了非诺贝特在高甘油三酯血症和肾功能不全患者中12周的药代动力学和安全性。
在这项4期、多中心、安慰剂对照、双盲、平行组、比较研究中，21例患者被随机分配至A组（估计肾小球滤过率[eGFR]＜30 mL/min/1.73m且未进行血液透析；非诺贝特组n = 4；安慰剂组，n = 2）、B组（血液透析；非诺贝特组，n = 4；安慰剂组，n = 1）和C组（eGFR≥30且＜60 mL/min/1.73m且未进行血液透析；非诺贝特组，n = 8；安慰剂组，n = 2），分别给予非诺贝特0.2 mg/天或安慰剂，持续12周。给药12周后测量非诺贝特给药间隔（τ）内的浓度-时间曲线下面积（AUC）。
非诺贝特在A + B组和C组中的AUC（几何均值）分别为7.333和7.991 ng·h/mL；在第12周时，A + B组与C组相比，非诺贝特AUC的几何均值比为0.92（90%置信区间[CI]：0.62，1.36）。90%CI的上限≤2.0（预定标准）。非诺贝特的AUC和最大血浆浓度在使用/未使用他汀类药物时没有一致的趋势。肾功能损害程度不影响不良事件的发生率。未观察到安全问题。
在重度肾功能不全患者中重复给予非诺贝特不会增加非诺贝特的暴露量。
