Baklouti Sarah, Concordet Didier, Borromeo Vitaliano, Pocar Paola, Scarpa Paola, Cagnardi Petra
INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France.
Laboratoire de Pharmacocinétique et Toxicologie, CHU de Toulouse, Toulouse, France.
Front Pharmacol. 2021 Apr 29;12:634404. doi: 10.3389/fphar.2021.634404. eCollection 2021.
Monitoring iohexol plasma clearance is considered a useful, reliable, and sensitive tool to establish glomerular filtration rate (GFR) and early stages of kidney disease in both humans and veterinary medicine. The assessment of GFR based on iohexol plasma clearance needs repeated blood sampling over hours, which is not easily attainable in a clinical setting. The study aimed to build a population pharmacokinetic (Pop PK) model to estimate iohexol plasma clearance in a population of dogs and based on this model, to indicate the best sampling times that enable a precise clearance estimation using a low number of samples. A Pop PK model was developed based on 5 iohexol plasma samples taken from 5 to 180 minutes (min) after an intravenous iohexol nominal dose of 64.7 mg/kg from 49 client-owned dogs of different breeds, sexes, ages, body weights, and clinical conditions (healthy or presenting chronic kidney disease CKD). The design of the best sampling times could contain either 1 or 2 or 3 sampling times. These were discretized with a step of 30 min between 30 and 180 min. A two-compartment Pop PK model best fitted the data; creatinine and kidney status were the covariates included in the model to explain a part of clearance variability. When 1 sample was available, 90 or 120 min were the best sampling times to assess clearance for healthy dogs with a low creatinine value. Whereas for dogs with CKD and medium creatinine value, the best sampling time was 150 or 180 min, for CKD dogs with a high creatinine value, it was 180 min. If 2 or 3 samples were available, several sampling times were possible. The method to define the best sampling times could be used with other Pop PK models as long as it is representative of the patient population and once the model is built, the use of individualized sampling times for each patient allows to precisely estimate the GFR.
监测碘海醇血浆清除率被认为是在人类和兽医学中建立肾小球滤过率（GFR）和肾病早期阶段的一种有用、可靠且敏感的工具。基于碘海醇血浆清除率评估GFR需要在数小时内反复采集血样，这在临床环境中不易实现。本研究旨在建立一个群体药代动力学（Pop PK）模型，以估计犬群体中的碘海醇血浆清除率，并基于该模型指出能够使用少量样本进行精确清除率估计的最佳采样时间。基于从49只不同品种、性别、年龄、体重和临床状况（健康或患有慢性肾病CKD）的客户拥有的犬只静脉注射64.7 mg/kg标称剂量碘海醇后5至180分钟采集的5份碘海醇血浆样本，开发了一个Pop PK模型。最佳采样时间的设计可以包含1次、2次或3次采样。这些采样时间在30至180分钟之间以30分钟为步长进行离散化。一个二室Pop PK模型最适合该数据；肌酐和肾脏状态是模型中纳入的协变量，用于解释清除率变异性的一部分。当只有1份样本时，90或120分钟是评估肌酐值低的健康犬清除率的最佳采样时间。而对于患有CKD且肌酐值中等的犬只，最佳采样时间是150或180分钟，对于肌酐值高的CKD犬只，是180分钟。如果有2或3份样本可用，则有几种采样时间可能。定义最佳采样时间的方法可与其他Pop PK模型一起使用，只要它代表患者群体，并且一旦建立模型，为每个患者使用个性化采样时间可以精确估计GFR。
