Soraluce Amaia, Barrasa Helena, Asín-Prieto Eduardo, Sánchez-Izquierdo Jose Ángel, Maynar Javier, Isla Arantxazu, Rodríguez-Gascón Alicia
Pharmacokinetics, Nanotechnology and Gene Therapy Group, Faculty of Pharmacy, Centro de Investigación Lascaray-ikergunea, University of the Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, Spain.
Intensive Care Unit, Araba University Hospital, 01004 Vitoria-Gasteiz, Spain.
Pharmaceutics. 2020 Jan 9;12(1):54. doi: 10.3390/pharmaceutics12010054.
Antimicrobial treatment in critically ill patients remains challenging. The aim of this study was to develop a population pharmacokinetic model for linezolid in critically ill patients and to evaluate the adequacy of current dosing recommendation (600 mg/12 h). Forty inpatients were included, 23 of whom were subjected to continuous renal replacement therapies (CRRT). Blood and effluent samples were drawn after linezolid administration at defined time points, and linezolid levels were measured. A population pharmacokinetic model was developed, using NONMEM 7.3. The percentage of patients that achieved the pharmacokinetic/pharmacodynamic (PK/PD) targets was calculated (AUC/MIC > 80 and 100% T). A two-compartment model best described the pharmacokinetics of linezolid. Elimination was conditioned by the creatinine clearance and by the extra-corporeal clearance if the patient was subjected to CRRT. For most patients, the standard dose of linezolid did not cover infections caused by pathogens with MIC ≥ 2 mg/L. Continuous infusion may be an alternative, especially when renal function is preserved.
对重症患者进行抗菌治疗仍然具有挑战性。本研究的目的是建立重症患者利奈唑胺的群体药代动力学模型，并评估当前给药推荐剂量（600mg/12小时）的合理性。纳入了40例住院患者，其中23例接受持续肾脏替代疗法（CRRT）。在利奈唑胺给药后的特定时间点采集血液和滤出液样本，并测定利奈唑胺水平。使用NONMEM 7.3建立群体药代动力学模型。计算达到药代动力学/药效学（PK/PD）目标（AUC/MIC>80和100%T）的患者百分比。二室模型最能描述利奈唑胺的药代动力学。如果患者接受CRRT，清除率受肌酐清除率和体外清除率的影响。对于大多数患者，利奈唑胺的标准剂量无法覆盖由MIC≥2mg/L的病原体引起的感染。持续输注可能是一种替代方法，尤其是在肾功能正常时。
