Population pharmacokinetic model of tranexamic acid in patients who undergo cardiac surgery with cardiopulmonary bypass.

IF 2.4 3区 医学 Q3 PHARMACOLOGY & PHARMACY European Journal of Clinical Pharmacology Pub Date : 2025-03-01 Epub Date: 2025-01-16 DOI:10.1007/s00228-025-03802-0
Tsuyoshi Nakai, Takahiro Tamura, Yasuhiro Miyagawa, Takayuki Inagaki, Masato Mutsuga, Shigeki Yamada, Kiyofumi Yamada, Kimitoshi Nishiwaki, Hiroyuki Mizoguchi
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Abstract

Purpose: Tranexamic acid (TXA) is widely used as an antifibrinolytic drug. However, studies to determine the optimal blood concentration of TXA have produced inconsistent results. During cardiac surgery, cardiopulmonary bypass (CPB) has serious effects on drug distribution, elimination, and plasma concentration. Therefore, we aimed to establish a population pharmacokinetics model of TXA in patients undergoing cardiac surgery with CPB that considers renal function as a covariate, thereby facilitating personalized treatment.

Methods: In total, 453 TXA plasma samples were prospectively collected from 77 patients who underwent cardiac surgery with CPB. Plasma concentrations were determined by ultra-performance liquid chromatography-tandem mass spectrometry. The population pharmacokinetic model of TXA was analyzed using nonlinear mixed-effects modeling.

Results: The two-compartment-based model with combined errors was determined as the best. The final model included the effect of bodyweight and CLcr may be summarized as V1 (L) = 12.77 × (bodyweight / 61.4)0.911, V2 (L) = 6.857, CL1 (L/h) = 3.263 × [CLcr (L/h) / 61.0]0.752, CL2 (L/h) = 2.859.

Conclusion: Patients who undergo cardiac surgery with CPB may require an adjusted dose of TXA tailored to CPB due to lower CL1 and increased V1. Our TXA population pharmacokinetic model may be useful for developing individualized dosing designs for TXA in patients who undergo cardiac surgery with CPB.

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心脏手术合并体外循环患者氨甲环酸的人群药代动力学模型。
目的:氨甲环酸(TXA)是一种广泛应用的抗纤溶药物。然而,确定TXA最佳血药浓度的研究产生了不一致的结果。在心脏手术中,体外循环(CPB)对药物分布、消除和血药浓度有严重影响。因此,我们旨在建立一个考虑肾功能作为协变量的心脏手术合并CPB患者TXA的人群药代动力学模型,从而促进个性化治疗。方法:前瞻性收集77例心脏手术合并CPB患者的453份TXA血浆样本。采用超高效液相色谱-串联质谱法测定血浆浓度。采用非线性混合效应模型分析TXA的群体药动学模型。结果:以双区室为基础的组合误差模型为最佳模型。考虑体重和CLcr影响的最终模型可归纳为V1 (L) = 12.77 ×(体重/ 61.4)0.911,V2 (L) = 6.857, CL1 (L/h) = 3.263 × [CLcr (L/h) / 61.0]0.752, CL2 (L/h) = 2.859。结论:由于较低的CL1和较高的V1,接受心脏手术的CPB患者可能需要调整剂量的TXA,以适应CPB。我们的TXA人群药代动力学模型可能有助于开发个体化的TXA给药方案,用于接受心脏手术合并CPB的患者。
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来源期刊
CiteScore
5.40
自引率
3.40%
发文量
170
审稿时长
3-8 weeks
期刊介绍: The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed. Data from animal experiments are accepted only in the context of original data in man reported in the same paper. EJCP will only consider manuscripts describing the frequency of allelic variants in different populations if this information is linked to functional data or new interesting variants. Highly relevant differences in frequency with a major impact in drug therapy for the respective population may be submitted as a letter to the editor. Straightforward phase I pharmacokinetic or pharmacodynamic studies as parts of new drug development will only be considered for publication if the paper involves -a compound that is interesting and new in some basic or fundamental way, or -methods that are original in some basic sense, or -a highly unexpected outcome, or -conclusions that are scientifically novel in some basic or fundamental sense.
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