Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Renji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine, 160# Pujian Road, Building 3, 12th Floor, Shanghai, 200127, China.
Clin Pharmacokinet. 2023 Nov;62(11):1581-1587. doi: 10.1007/s40262-023-01300-z. Epub 2023 Sep 15.
This study aimed to assess the pharmacokinetics of henagliflozin in dialysis patients with diabetes.
In this prospective, randomized, open-label study where 10 hemodialysis and 10 peritoneal dialysis patients with diabetes were randomized in a 1:1:1:1 ratio to oral administration of henagliflozin in doses of 5 and 10 mg/day. The pharmacokinetics of a single dose of henagliflozin on Days 1 and 2, the minimum plasma concentration (C) of the steady state on Day 10, and single hemodialysis clearance of henagliflozin were measured.
The mean values of C were 70.2-77.0 ng/mL and 105-143 ng/mL in the 5 mg and 10 mg henagliflozin groups, respectively; the mean values of AUC were 777-811 hng/mL and 1290-1730 hng/mL in the 5 mg and 10 mg henagliflozin groups, respectively. The median T values ranged from 1 to 3 h across the dose range. The mean values of T of henagliflozin were 14.1-14.5 and 16.2-21.0 h in the 5 mg and 10 mg groups, respectively. The C values of the steady state in dialysis patients taking 5 mg and 10 mg of henagliflozin were 15.0 ± 4.4 ng/mL and 26.8 ± 16.3 ng/mL, respectively, which were 123.8% and 131.0% higher than those in diabetic patients with normal renal function, respectively. Henagliflozin concentration was decreased by 1.1% after hemodialysis treatment. No treatment-related serious adverse events or discontinuations occurred.
Henagliflozin at the current recommended dosage may be safe, although it is possible to result in slight accumulation in patients on dialysis.
Chinese Clinical Trial Registry number ChiCTR2200062872. The date of registration: August 22, 2022.
本研究旨在评估在患有糖尿病的透析患者中依帕列净的药代动力学。
这是一项前瞻性、随机、开放标签研究，10 名糖尿病血液透析和 10 名糖尿病腹膜透析患者以 1:1:1:1 的比例随机接受依帕列净 5mg 和 10mg 每日口服治疗。在第 1 天和第 2 天测量单次给药的依帕列净药代动力学、第 10 天的稳态最小血浆浓度（C）和单次血液透析清除率。
依帕列净 5mg 和 10mg 组的 C 平均值分别为 70.2-77.0ng/mL 和 105-143ng/mL；AUC 平均值分别为 777-811hng/mL 和 1290-1730hng/mL。剂量范围内 T 值中位数为 1-3 小时。依帕列净 T 值的平均值分别为 14.1-14.5 和 16.2-21.0 小时。接受依帕列净 5mg 和 10mg 的透析患者稳态 C 值分别为 15.0±4.4ng/mL 和 26.8±16.3ng/mL，分别比肾功能正常的糖尿病患者高 123.8%和 131.0%。血液透析治疗后依帕列净浓度降低 1.1%。未发生与治疗相关的严重不良事件或停药。
在目前推荐的剂量下，依帕列净可能是安全的，尽管在透析患者中可能会导致轻微的蓄积。
中国临床试验注册中心编号 ChiCTR2200062872。注册日期：2022 年 8 月 22 日。
