Martínez-Casanova Javier, Esteve-Pitarch Erika, Colom-Codina Helena, Gumucio-Sanguino Víctor Daniel, Cobo-Sacristán Sara, Shaw Evelyn, Maisterra-Santos Kristel, Sabater-Riera Joan, Pérez-Fernandez Xosé L, Rigo-Bonnin Raül, Tubau-Quintano Fe, Carratalà Jordi, Padullés-Zamora Ariadna
Pharmacy Department, Hospital Universitari de Bellvitge, 08907 Hospitalet de Llobregat, Spain.
Farmacoteràpia, Farmacogenètica i Tecnologia Farmacèutica, Institut d'Investigació Biomèdica de Bellvitge, IDIBELL, 08907 Hospitalet de Llobregat, Spain.
Antibiotics (Basel). 2023 Mar 7;12(3):531. doi: 10.3390/antibiotics12030531.
Critically ill patients undergo significant pathophysiological changes that affect antibiotic pharmacokinetics. Piperacillin/tazobactam administered by continuous infusion (CI) improves pharmacokinetic/pharmacodynamic (PK/PD) target attainment. This study aimed to characterize piperacillin PK after CI administration of piperacillin/tazobactam in critically ill adult patients with preserved renal function and to determine the empirical optimal dosing regimen. A total of 218 piperacillin concentrations from 106 patients were simultaneously analyzed through the population PK approach. A two-compartment linear model best described the data. Creatinine clearance (CL) estimated by CKD-EPI was the covariate, the most predictive factor of piperacillin clearance (CL) interindividual variability. The mean (relative standard error) parameter estimates for the final model were: CL: 12.0 L/h (6.03%); central and peripheral compartment distribution volumes: 20.7 L (8.94%) and 62.4 L (50.80%), respectively; intercompartmental clearance: 4.8 L/h (26.4%). For the PK/PD target of 100% T, 12 g of piperacillin provide a probability of target attainment > 90% for MIC < 16 mg/L, regardless of CL, but higher doses are needed for MIC = 16 mg/L when CL > 100 mL/min. For 100% T, the highest dose (24 g/24 h) was not sufficient to ensure adequate exposure, except for MICs of 1 and 4 mg/L. Our model can be used as a support tool for initial dose guidance and during therapeutic drug monitoring.
重症患者会经历显著的病理生理变化，这些变化会影响抗生素的药代动力学。持续输注（CI）哌拉西林/他唑巴坦可改善药代动力学/药效学（PK/PD）目标的达成。本研究旨在描述在肾功能正常的重症成年患者中CI给予哌拉西林/他唑巴坦后哌拉西林的药代动力学特征，并确定经验性的最佳给药方案。通过群体药代动力学方法对106例患者的218个哌拉西林浓度进行了同步分析。二室线性模型最能描述这些数据。用CKD-EPI估算的肌酐清除率（CL）是协变量，是哌拉西林清除率（CL）个体间差异的最具预测性的因素。最终模型的平均（相对标准误差）参数估计值为：CL：12.0 L/h（6.03%）；中央室和外周室分布容积分别为：20.7 L（8.94%）和62.4 L（50.80%）；室间清除率：4.8 L/h（26.4%）。对于100%T的PK/PD目标，无论CL如何，12 g哌拉西林对于MIC<16 mg/L的目标达成概率>90%，但当CL>100 mL/min且MIC = 16 mg/L时需要更高剂量。对于100%T，最高剂量（24 g/24 h）不足以确保足够的暴露，MIC为1和4 mg/L时除外。我们的模型可作为初始剂量指导和治疗药物监测期间的支持工具。
