Abramavicius Silvijus, Galaune Vaidotas, Tunaityte Agile, Vitkauskiene Astra, Gumbrevicius Gintautas, Radzeviciene Aurelija, Maciulaitis Romaldas
Laboratory of Preclinical Drug, Investigation Institute of Cardiology, Lithuanian University of Health Sciences, LT-47181 Kaunas, Lithuania.
Department of Laboratory Medicine, Lithuanian University of Health Sciences, LT-47181 Kaunas, Lithuania.
Antibiotics (Basel). 2021 Feb 4;10(2):158. doi: 10.3390/antibiotics10020158.
The glomerular filtration rate (GFR), according to which the drug dose for patients with chronic kidney disease (CKD) is adjusted, is computed with estimators (eGFR) that are developed specifically for CKD. These particular types of estimators are also used in population pharmacokinetic (pop PK) modelling in drug development. Similar approaches without scientific validation have been proposed for patients with acute kidney injury (AKI), yet it is uncertain which specific eGFR should be used for drug dosing or in pop PK models in patients with AKI. In our study, we included 34 patients with AKI and vancomycin (VCM) treatment, and we built both individual PK and pop PK (non-linear mixed-effects, one-compartment) models to see which eGFR estimator is the best covariate. In these models different eGFRs (Cockcroft-Gault, MDRD, CKD-EPI 2009, Jelliffe and Jelliffe, Chen et al., and Yashiro et al. 2013) were used. We included six additional patients to validate the final pop PK model. All eGFRs underrate the true renal clearance in the AKI, so we created pop PK models for VCM dosing in AKI with all eGFRs, to discover that the most accurate model was the one with the Cockcroft-Gault estimator. Since the eGFRs underestimate the true renal clearance in AKI, they are inaccurate for clinical drug dosing decisions, with the exception of the Cockcroft-Gault one, which is appropriate for the pop PK models intended for drug development purposes in AKI.
肾小球滤过率（GFR）是调整慢性肾脏病（CKD）患者药物剂量的依据，它通过专门为CKD开发的估算器（eGFR）来计算。这些特定类型的估算器也用于药物研发中的群体药代动力学（pop PK）建模。对于急性肾损伤（AKI）患者，有人提出了类似但未经科学验证的方法，然而，对于AKI患者的药物给药或pop PK模型中应使用哪种特定的eGFR尚不确定。在我们的研究中，我们纳入了34例接受万古霉素（VCM）治疗的AKI患者，并建立了个体药代动力学和pop PK（非线性混合效应，单室）模型，以确定哪种eGFR估算器是最佳协变量。在这些模型中使用了不同的eGFR（Cockcroft-Gault、MDRD、CKD-EPI 2009、Jelliffe和Jelliffe、Chen等人以及Yashiro等人2013年的方法）。我们又纳入了6例患者以验证最终的pop PK模型。所有的eGFR都低估了AKI患者的真实肾脏清除率，因此我们用所有的eGFR建立了AKI患者VCM给药的pop PK模型，发现最准确的模型是采用Cockcroft-Gault估算器的模型。由于eGFR在AKI中低估了真实的肾脏清除率，它们对于临床药物给药决策是不准确的，但Cockcroft-Gault估算器除外，它适用于AKI中用于药物研发目的的pop PK模型。
