连续肾脏替代治疗患者应用贝叶斯预测法制定万古霉素剂量个体化方案
Development of Vancomycin Dose Individualization Strategy by Bayesian Prediction in Patients Receiving Continuous Renal Replacement Therapy.
机构信息
Department of Pharmacy, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto city, Kumamoto, Japan.
Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto city, Kumamoto, Japan.
出版信息
Pharm Res. 2020 May 28;37(6):108. doi: 10.1007/s11095-020-02820-0.
PURPOSE
Vancomycin (VCM) concentration is often out of therapeutic range (10-20 μg/ml) in patients receiving continuous renal replacement therapy (CRRT). The purposes of this study were to develop a practical VCM population pharmacokinetic (PPK) model and to evaluate the potential of Bayesian prediction-based therapeutic drug monitoring (Bayes-TDM) in VCM dose individualization for patients receiving CRRT.
METHODS
We developed a VCM PPK model using 80 therapeutic concentrations in 17 patients receiving CRRT. Bayes-TDM with the VCM PPK model was evaluated in 23 patients after PPK modeling.
RESULTS
We identified the covariates reduced urine output (RUO, <0.5 ml/kg/h) and effluent flow rate of CRRT for the VCM PPK model. The mean VCM non CRRT clearance (CL) was 2.12 l/h. RUO lowered CL to 0.34 l/h. The volume of distribution was 91.3 l/70 kg. The target concentration attainment rate by Bayes-TDM was higher (87.0%) than that by the PPK modeling period (53.8%, P = 0.046). The variance of the second measured concentrations by the Bayes-TDM was lower (11.5, standard deviation: 3.4 μg/ml) than that by the PPK modeling period (50.5, standard deviation: 7.1 μg/ml, P = 0.003).
CONCLUSIONS
Bayes-TDM could be a useful tool for VCM dose individualization in patients receiving CRRT.
目的
在接受连续肾脏替代治疗（CRRT）的患者中，万古霉素（VCM）的浓度经常超出治疗范围（10-20μg/ml）。本研究的目的是开发一种实用的 VCM 群体药代动力学（PPK）模型，并评估基于贝叶斯预测的治疗药物监测（Bayes-TDM）在 VCM 剂量个体化中的潜力，以用于接受 CRRT 的患者。
方法
我们使用 17 名接受 CRRT 的患者的 80 个治疗浓度开发了 VCM PPK 模型。在 PPK 建模后，我们对 23 名患者进行了 VCM PPK 模型的贝叶斯 TDM 评估。
结果
我们确定了降低尿液输出（RUO，<0.5ml/kg/h）和 CRRT 流出率的协变量，用于 VCM PPK 模型。VCM 非 CRRT 清除率（CL）的平均值为 2.12l/h。RUO 将 CL 降低至 0.34l/h。分布容积为 91.3l/70kg。贝叶斯 TDM 的目标浓度达标率（87.0%）高于 PPK 建模期（53.8%，P=0.046）。贝叶斯 TDM 第二次测量浓度的方差（11.5，标准差：3.4μg/ml）低于 PPK 建模期（50.5，标准差：7.1μg/ml，P=0.003）。
结论
贝叶斯 TDM 可能是 CRRT 患者 VCM 剂量个体化的有用工具。
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