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Crit Care:接受CRRT的重症患者使用替加环素需要调整剂量吗?

2019-02-21 不详 网络

2018年12月,德国学者发表在《Crit Care》的一项群体药物代谢动力学研究,考察了替加环素用于接受连续肾脏替代治疗(CRRT)的重症患者的效果。

2018年12月,德国学者发表在《Crit Care》的一项群体药物代谢动力学研究,考察了替加环素用于接受连续肾脏替代治疗(CRRT)的重症患者的效果。

背景:替加环素是重症监护病房(ICU)中多药耐药菌造成的感染患者重要的抗感染治疗选择。急性肾损伤(AKI)是ICU中需要CRRT患者的常见并发症,但是缺乏接受CRRT治疗的患者的替加环素的药物代谢动力学数据。

方法:纳入了11名主要为腹腔内感染的患者,这些患者接受连续静脉-静脉血液透析(CVVHD,8人)或血液透析滤过(CVVHDF,3人)。根据丰富采样计划,收集血浆和流出物样本。通过超滤和高效液相色谱(HPLC)-UV,确定总体和游离替加环素。使用NONMEM 7.4建立群体药物代谢动力学模型,用于确定药物代谢动力学参数以及CVVHD和CVVHDF的清除率。药代学/药效学目标实现分析用于探讨CRRT中替加环素剂量调整的潜在需求。

结果:二室群体药物代谢动力学(PK)模型适合同时描述替加环素的血浆PK和滤出液测量。由于CVVHD和CVVHDF分别具有较高的平均饱和系数0.79和0.90,并且位于替加环素浓度依赖的非结合分数范围内(45%~94%),因此替吉环素透析能力较高。然而,与18.3L/h的CLbody(生理部分的总清除率)相比,CRRT对替加环素清除率(CL)的贡献仅为中等(CL CVVHD:1.69L/h,CL CVVHDF:2.71L/h)。将胆红素确定为CLbody的协变量,将观察到的CLbody个体间变异性从58.6%降低到43.6%。对于最小抑菌浓度(MIC)≤0.5mg/L,CRRT治疗腹部感染的目标实现的概率≥0.88,与无AKI的患者相似。

结论:尽管具有较高的透析性,但透析清除对替加环素清除率只显示出较小影响,位于无AKI患者的肾脏清除率的范围内。在CRRT中,不必要调整替加环素剂量。

原始出处:

Broeker A, et al. Tigecycline in critically ill patients on continuous renal replacement therapy: a population pharmacokinetic study. Crit Care. 2018 Dec 17;22(1):341. doi: 10.1186/s13054-018-2278-4.

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