Wu Yunjiao, Allegaert Karel, Flint Robert B, Simons Sinno H P, Krekels Elke H J, Knibbe Catherijne A J, Völler Swantje
Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands.
AAPS J. 2022 Feb 25;24(2):38. doi: 10.1208/s12248-022-00688-z.
Describing glomerular filtration rate (GFR) maturation across the heterogeneous population of preterm and term neonates and infants is important to predict the clearance of renally cleared drugs. This study aims to describe the GFR maturation in (pre)term neonates and young infants (PNA < 90 days) using individual inulin clearance data (CL). To this end, published GFR maturation models were evaluated by comparing their predicted GFR with CL retrieved from literature. The best model was subsequently optimized in NONMEM V7.4.3 to better fit the CL values. Our study evaluated seven models and collected 381 individual CL values from 333 subjects with median (range) birthweight (BWb) 1880 g (580-4950), gestational age (GA) 34 weeks (25-43), current weight (CW) 1890 g (480-6200), postnatal age (PNA) 3 days (0-75), and CL 2.20 ml/min (0.43-17.90). The De Cock 2014 model (covariates: BWb and PNA) performed the best in predicting CL, followed by the Rhodin 2009 model (covariates: CW and postmenstrual age). The final optimized model shows that GFR at birth is determined by BWb, thereafter the maturation rate of GFR is dependent on PNA and GA, with a higher GA showing an overall faster maturation. To conclude, using individual CL data, we found that a model for neonatal GFR requires a distinction between prenatal maturation quantified by BWb and postnatal maturation. To capture postnatal GFR maturation in (pre)term neonates and young infants, we developed an optimized model in which PNA-related maturation was dependent on GA.
描述早产和足月新生儿及婴儿异质性群体的肾小球滤过率（GFR）成熟情况对于预测经肾脏清除药物的清除率很重要。本研究旨在使用个体菊粉清除率数据（CL）描述（早产）足月新生儿和幼儿（出生后年龄<PNA<90天）的GFR成熟情况。为此，通过将已发表的GFR成熟模型预测的GFR与从文献中检索到的CL进行比较来评估这些模型。随后在NONMEM V7.4.3中对最佳模型进行优化，以更好地拟合CL值。我们的研究评估了七个模型，并收集了333名受试者的381个个体CL值，这些受试者的中位（范围）出生体重（BWb）为1880 g（580 - 4950）、胎龄（GA）为34周（25 - 43）、当前体重（CW）为1890 g（480 - 6200）、出生后年龄（PNA）为3天（0 - 75）以及CL为2.20 ml/min（0.43 - 17.90）。De Cock 2014模型（协变量：BWb和PNA）在预测CL方面表现最佳，其次是Rhodin 2009模型（协变量：CW和月经后年龄）。最终优化模型表明，出生时的GFR由BWb决定，此后GFR的成熟率取决于PNA和GA，GA越高总体成熟速度越快。总之，使用个体CL数据，我们发现新生儿GFR模型需要区分由BWb量化的产前成熟和产后成熟。为了捕捉（早产）足月新生儿和幼儿产后GFR的成熟情况，我们开发了一个优化模型，其中与PNA相关的成熟取决于GA。
