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

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 CL cr may be summarized as V 1 (L) = 12.77 × (bodyweight / 61.4) 0.911 , V 2 (L) = 6.857, CL 1 (L/h) = 3.263 × [CL cr (L/h) / 61.0] 0.752 , CL 2 (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 CL 1 and increased V 1 . 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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