Certara UK Ltd, Simcyp Division, Sheffield, UK.
Centre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
J Clin Pharmacol. 2021 Feb;61(2):159-171. doi: 10.1002/jcph.1725. Epub 2020 Sep 3.
Glomerular filtration rate (GFR) is an important measure of renal function. Various models for its maturation have recently been compared; however, these have used markers, which are subject to different renal elimination processes. Inulin clearance data (a purer probe of GFR) collected from the literature were used to determine age-related changes in GFR aspects of renal drug excretion in pediatrics. An ontogeny model was derived using a best-fit model with various combinations of covariates such as postnatal age, gestational age at birth, and body weight. The model was applied to the prediction of systemic clearance of amikacin, gentamicin, vancomycin, and gadobutrol. During neonatal life, GFR increased as a function of both gestational age at birth and postnatal age, hence implying an impact of birth and a discrepancy in GFR for neonates with the same postmenstrual age depending on gestational age at birth (ie, neonates who were outside the womb longer had higher GFR, on average). The difference in GFR between pre-term and full-term neonates with the same postmenstrual age was negligible from beyond 1.25 years. Considering both postnatal age and gestational age at birth in GFR ontogeny models is important because postmenstrual age alone ignores the impact of birth. Most GFR models use covariates of body size in addition to age. Therefore, prediction from these models will also depend on the change in anthropometric characteristics with age. The latter may not be similar in various ethnic groups, and this makes the head-to-head comparison of models very challenging.
肾小球滤过率(GFR)是衡量肾功能的重要指标。最近,人们对其成熟的各种模型进行了比较;然而,这些模型使用的标志物受到不同的肾脏消除过程的影响。本研究使用文献中收集的菊粉清除数据(一种更纯净的 GFR 探针)来确定儿科肾药物排泄中 GFR 方面的年龄相关变化。使用具有各种协变量(如出生后年龄、出生时胎龄和体重)的最佳拟合模型来推导发育模型。该模型应用于预测阿米卡星、庆大霉素、万古霉素和钆布醇的全身清除率。在新生儿期,GFR 的增加是出生时胎龄和出生后年龄的函数,因此这意味着出生的影响以及具有相同胎龄的新生儿 GFR 的差异取决于出生时的胎龄(即,在子宫外时间较长的新生儿平均 GFR 较高)。具有相同胎龄但胎龄不同的早产儿和足月儿之间的 GFR 差异从 1.25 岁以后可以忽略不计。在 GFR 发育模型中考虑出生后年龄和出生时胎龄很重要,因为仅胎龄会忽略出生的影响。大多数 GFR 模型除了年龄外还使用身体大小的协变量。因此,这些模型的预测还取决于与年龄相关的人体测量特征的变化。后者在不同种族群体中可能并不相似,这使得模型的直接比较极具挑战性。