Pharmacokinetics and Safety of Pemafibrate in Patients with both Dyslipidemia and Severe Renal Impairment: A Phase 4 Study.

IF 3 2区医学 Q2 PERIPHERAL VASCULAR DISEASE

Journal of atherosclerosis and thrombosis Pub Date : 2024-09-05 DOI:10.5551/jat.64887

Shun Ishibashi, Hidenori Arai, Koutaro Yokote, Eiichi Araki, Mao Watanabe, Michiko Nakanishi, Yuichi Makinose, Hideki Suganami, Yuji Kurihara, Shizuya Yamashita

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Abstract

Aims: 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.

Methods: 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/1.73m² without hemodialysis; pemafibrate n=4; placebo, n=2), B (hemodialysis; pemafibrate, n=4; placebo, n=1), and C (eGFR ≥ 30 and ＜60 mL/min/1.73m² without hemodialysis; pemafibrate, n=8; placebo, n=2) for 12 weeks. Area under the concentration vs time curve within the dosing interval (τ) (AUC_τ) of pemafibrate was measured after 12-week administration.

Results: The AUC_τ (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_τ 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_τ 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.

Conclusion: Pemafibrate repeated administration in patients with severe renal impairment did not increase pemafibrate exposure.

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同时患有血脂异常和严重肾功能损害的患者服用培马贝特的药代动力学和安全性：4 期研究。

目的：根据包装说明书，尽管培马贝特可通过胆汁排泄，但严重肾功能损害患者禁用培马贝特。为了验证这一点，我们对高甘油三酯血症和肾功能损害患者服用培马贝特 12 周的药代动力学和安全性进行了评估：在这项 4 期、多中心、安慰剂对照、双盲、平行组比较研究中，21 名患者被随机分配到 A 组（估计肾小球滤过率 [eGFR] ＜30 mL/min/1.B 组（血液透析；培马贝特，n=4；安慰剂，n=1）和 C 组（eGFR ≥ 30 和＜ 60 毫升/分钟/1.73 平方米，无血液透析；培马贝特，n=8；安慰剂，n=2），为期 12 周。服用 12 周后，测量了培马贝特在给药间隔 (τ) 内的浓度与时间曲线下的面积（AUCτ）：A+B组和C组的培马贝特AUCτ（几何平均）分别为7.333和7.991纳克-小时/毫升；12周时，A+B组与C组的培马贝特AUCτ几何平均比为0.92（90%置信区间[CI]：0.62，1.36）。90%置信区间的上限≤2.0（预定标准）。使用/不使用他汀类药物时，培马贝特的AUCτ和最大血浆浓度没有一致的趋势。肾功能损害程度不影响不良事件的发生率。结论严重肾功能损害患者重复服用培马贝特不会增加培马贝特的暴露量。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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