Laboratory of Atherosclerosis and Vascular Biology (Aterolab), Cardiology Division, University of Campinas (Unicamp), Campinas, Brazil.
Laboratory for Evaluation of Mineral and Bone Disorders in Nephrology (LEMON), Nephrology Division, University of Campinas (Unicamp), Campinas, Brazil.
Clin J Am Soc Nephrol. 2023 Aug 1;18(8):1051-1058. doi: 10.2215/CJN.0000000000000196. Epub 2023 May 25.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors attenuate incident cardiovascular outcomes, irrespective of baseline GFR, in conservatively managed CKD. As this condition inexorably progresses to demanding KRT, drug withdrawal is supported by the current lack of evidence of safety of SGLT2 inhibitors in dialysis.
This study was a prospective, single-center, open-label trial ( ClinicalTrials.gov identifier: NCT05343078 ) aimed at assessing the pharmacokinetic properties and safety of dapagliflozin in patients with kidney failure on regular dialysis regimens compared with those with type 2 diabetes and age- and sex-matched controls with normal kidney function. Peripheral blood samples were collected from both groups every 30 minutes for 4 hours and again after 48 hours after ingestion of dapagliflozin 10 mg, which occurred immediately before dialysis session initiation in the kidney failure group. This protocol occurred in drug-naïve patients and again after six daily doses of dapagliflozin to assess whether the drug had accumulated. The plasma and dialysate levels of dapagliflozin at each time point were determined by liquid chromatography and used to calculate pharmacokinetics parameters (peak concentration [C max ] and area under the plasma concentration-versus-time curve) for each participant.
Dapagliflozin C max was 117 and 97.6 ng/ml in the kidney failure and control groups, respectively, whereas the corresponding accumulation ratios were 26.7% and 9.5%. No serious adverse events were reported for either group. Dapagliflozin recovered from dialysate corresponded to 0.10% of the administered dose.
In patients with kidney failure on dialysis, dapagliflozin was well tolerated, was slightly dialyzable, and had nonaccumulating pharmacokinetic properties.
Pharmacokinetics and Dialyzability of Dapagliflozin in Dialysis Patients (DARE-ESKD 1), NCT05343078.
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂可降低保守治疗的 CKD 患者的心血管事件发生率，无论基线肾小球滤过率（GFR）如何。由于这种情况不可避免地进展到需要进行肾脏替代治疗（KRT），目前缺乏 SGLT2 抑制剂在透析患者中使用安全性的证据，因此支持药物停药。
这是一项前瞻性、单中心、开放标签试验（ClinicalTrials.gov 标识符：NCT05343078），旨在评估达格列净在接受常规透析方案治疗的肾衰竭患者中的药代动力学特征和安全性，与 2 型糖尿病患者以及年龄和性别匹配的肾功能正常的对照组进行比较。两组患者在服用达格列净 10mg 后 30 分钟采集外周血样本，4 小时后再次采集，然后在肾衰竭组开始透析前立即采集。该方案在药物初治患者中进行，并在再次给予达格列净 6 天剂量后进行评估，以确定药物是否有蓄积。通过液相色谱法测定每个时间点的达格列净的血浆和透析液水平，并用于计算每位参与者的药代动力学参数（峰浓度 [C max ]和血浆浓度-时间曲线下面积）。
肾衰竭组和对照组的达格列净 C max 分别为 117 和 97.6ng/ml，相应的蓄积率分别为 26.7%和 9.5%。两组均未报告严重不良事件。从透析液中回收的达格列净相当于给予剂量的 0.10%。
在接受透析的肾衰竭患者中，达格列净耐受良好，可轻度透析，且具有非蓄积的药代动力学特征。
达格列净在透析患者中的药代动力学和可透析性（DARE-ESKD 1），NCT05343078。
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