Department of Laboratory Hematology, Pontchaillou University Hospital of Rennes, Rennes, France; Institut de Recherche en Santé, Environnement et Travail (IRSET)-Institut National de la Santé et de la Recherche Médicale (INSERM)-1085, University of Rennes, Rennes, France.
Institut de Recherche en Santé, Environnement et Travail (IRSET)-Institut National de la Santé et de la Recherche Médicale (INSERM)-1085, University of Rennes, Rennes, France; Department of Anesthesia and Critical Care, Pontchaillou University Hospital of Rennes, Rennes, France.
J Thromb Haemost. 2024 Oct;22(10):2864-2872. doi: 10.1016/j.jtha.2024.07.006. Epub 2024 Jul 15.
Tinzaparin could be easier to manage than unfractionated heparin in patients with severe renal impairment. However, clinical and pharmacologic data regarding its use in such patients are lacking.
The aims of this study were to determine, in patients with estimated glomerular filtration rate (eGFR) of <30 mL.min⁻, tinzaparin pharmacokinetics (PK) parameters using a population PK approach and bleeding and thrombotic complications.
We performed a retrospective observational single-center study, including in-patients with eGFR of <30 mL.min⁻ receiving prophylactic (4500 IU.d⁻) or therapeutic (175 IU.kg⁻.d⁻) tinzaparin. Measured anti-Xa levels were analyzed using a nonlinear mixed-effects modeling approach. Individual predicted tinzaparin exposure markers at steady state were calculated for each patient and dosing regimen. The PK was also evaluated through Monte Carlo simulations based on the final covariate model parameter estimates.
Over a 22-month period, 802 tinzaparin treatment periods in 623 patients were analyzed: two-thirds received a prophylactic dose, 66% had an eGFR of <20 mL.min⁻, and 25% were on renal replacement therapy. In patients for whom anti-Xa measurements were performed (n = 199; 746 values), PK parameters, profiles, and maximum plasma concentrations were comparable with those in patients without renal impairment or in healthy volunteers. In the whole population, major bleeding occurred in 2.4% and 3.5% of patients receiving prophylactic and therapeutic doses over a median 9- and 7-day treatment period, respectively. No patients had thrombotic complications.
Tinzaparin PK parameters and profiles were not affected by renal impairment. This suggests that tinzaparin, at therapeutic or prophylactic dose, could be an alternative to unfractionated heparin in hospitalized patients with severe renal impairment.
对于严重肾功能不全的患者，相比未分级肝素，亭扎肝素可能更容易管理。然而，此类患者使用亭扎肝素的临床和药理学数据尚缺乏。
本研究旨在通过群体药代动力学（PK）方法确定估算肾小球滤过率（eGFR）<30 mL/min 的患者中，亭扎肝素的 PK 参数，并评估出血和血栓并发症。
我们开展了一项回顾性单中心研究，包括接受预防剂量（4500 IU/d）或治疗剂量（175 IU/kg/d）亭扎肝素的 eGFR<30 mL/min 的住院患者。使用非线性混合效应模型分析测定的抗 Xa 水平。为每位患者和每种给药方案计算个体稳态预测的亭扎肝素暴露标志物。还基于最终协变量模型参数估计值，通过蒙特卡罗模拟评估 PK。
在 22 个月期间，分析了 623 例患者的 802 个亭扎肝素治疗期：三分之二的患者接受预防剂量，66%的患者 eGFR<20 mL/min，25%的患者接受肾脏替代治疗。在进行抗 Xa 测量的患者（n=199；746 个值）中，PK 参数、图谱和最大血浆浓度与肾功能正常或健康志愿者中的患者相似。在全人群中，接受预防剂量和治疗剂量的患者在中位 9 天和 7 天治疗期间分别有 2.4%和 3.5%发生大出血。无患者发生血栓并发症。
肾功能不全并未影响亭扎肝素的 PK 参数和图谱。这表明，在严重肾功能不全的住院患者中，亭扎肝素无论作为治疗剂量还是预防剂量，都可能替代未分级肝素。
