The aim of this study was to develop a population pharmacokinetics (PK) model for vancomycin and to evaluate its pharmacodynamic target attainment in adults on extracorporeal membrane oxygenation (ECMO). After a single 1,000-mg dose of vancomycin, samples were collected 9 times per patient prospectively. A population PK model was developed using a nonlinear mixed-effect model. The probability of target attainment (PTA) of vancomycin was evaluated for various dosing strategies using Monte Carlo simulation. The ratio of the area under the vancomycin concentration-time curve at steady state over 24 h to the MIC (AUC/MIC ratio) was investigated by applying the vancomycin breakpoint distribution of MICs for methicillin-resistant Staphylococcus aureus. A total of 22 adult patients with 194 concentration measurements were included. The population PK was best described by a three-compartment model with a proportional residual error model. Vancomycin clearance and steady-state volume of distribution were 4.01 liters/h (0.0542 liters/h/kg) and 29.6 liters (0.400 liters/kg), respectively. If the treatment target AUC/MIC value was only ≥400, a total daily dose of 3 to 4 g would be optimal (PTA of ≥90%) for patients with normal renal function (estimated glomerular filtration rate [eGFR] = 60 to 120 ml/min/1.73 m²) when the MIC was presumed to be 1 mg/liter. However, AUC/MIC values of 400 to 600 were difficult to attain with any dosing strategy regardless of MIC and eGFR. Thus, it is hard to achieve efficacy and safety targets in patients on ECMO using the population dosing approach with Monte Carlo simulations, and therapeutic drug monitoring should be implemented in these patients.

中文翻译：

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在体外膜氧合下成人万古霉素的药代动力学和药效学目标达成的前瞻性队列研究

这项研究的目的是开发万古霉素的群体药代动力学（PK）模型，并评估其在体外膜氧合（ECMO）上对成人的药效学指标。单次服用1000毫克万古霉素后，每位患者预期收集9次样品。使用非线性混合效应模型开发了种群PK模型。使用蒙特卡洛模拟评估了各种给药策略的万古霉素达到目标（PTA）的可能性。通过应用耐甲氧西林金黄色葡萄球菌的MIC的万古霉素断裂点分布，研究了24小时内稳态下万古霉素浓度-时间曲线下面积与MIC的比率（AUC / MIC比率）。总共包括22位成年患者，进行194次浓度测量。人口PK最好用三室模型和比例残差模型来描述。万古霉素清除率和稳态分布体积分别为4.01升/小时（0.0542升/小时/ kg）和29.6升（0.400升/ kg）。如果治疗目标AUC / MIC值仅≥400，则对于肾功能正常（估计肾小球滤过率[eGFR] = 60至120）的患者，最佳每日总剂量为3至4 g（PTA≥90％） ml /分钟/1.73 m ²），假设MIC设为1 mg / L。然而，无论MIC和eGFR如何，任何剂量策略都难以获得400至600的AUC / MIC值。因此，难以通过使用蒙特蒙特卡罗模拟的群体给药方法在ECMO患者上实现疗效和安全性目标，因此应在这些患者中实施治疗性药物监测。