Ezuruike Udoamaka, Blenkinsop Alexander, Pansari Amita, Abduljalil Khaled
Certara UK Limited (Simcyp Division), Sheffield, United Kingdom.
Front Pediatr. 2022 Mar 3;10:841495. doi: 10.3389/fped.2022.841495. eCollection 2022.
Adequate prediction of fetal exposure of drugs excreted by the kidney requires the incorporation of time-varying renal function parameters into a pharmacokinetic model. Published data on measurements of fetal urinary production rate (FUPR) and creatinine at various gestational ages were collected and integrated for prediction of the fetal glomerular filtration rate (GFR). The predicted GFR values were then compared to neonatal values recorded at birth. Collected data for FUPR across different gestational ages using both 3D ( = 517) and 2D ( = 845) ultrasound methods showed that 2D techniques yield significantly lower estimates of FUPR than 3D ( < 0.0001). A power law function was shown to best capture the change in FUPR with fetal age (FA) for both 2D ( ); and 3D ( ) data. The predicted FUPR based on the observed 3D data was shown to be strongly linearly related ( = 0.95) to measured values of amniotic creatinine concentration ( = 664). The FUPR data together with creatinine levels in the fetal urine and serum resulted in median predicted fetal GFR values of 0.47, 1.2, 2.5, and 4.9 ml/min at 23, 28, 33, and 38 weeks of fetal age (50% CV), respectively. These values are in good agreement with neonatal values observed immediately at birth. The derived FUPR and creatinine functions can be utilized to assess fetal renal maturation and predict fetal renal clearance.
要充分预测经肾脏排泄药物的胎儿暴露情况,需要将随时间变化的肾功能参数纳入药代动力学模型。收集并整合了已发表的关于不同胎龄胎儿尿生成率(FUPR)和肌酐测量的数据,以预测胎儿肾小球滤过率(GFR)。然后将预测的GFR值与出生时记录的新生儿值进行比较。使用三维(n = 517)和二维(n = 845)超声方法收集的不同胎龄FUPR数据显示,二维技术得出的FUPR估计值显著低于三维技术(P < 0.0001)。对于二维(R² = )和三维(R² = )数据,幂律函数被证明最能体现FUPR随胎龄(FA)的变化。基于观察到的三维数据预测的FUPR与羊水肌酐浓度测量值(n = 664)呈强线性相关(R = 0.95)。FUPR数据与胎儿尿液和血清中的肌酐水平相结合,得出胎龄23、28、33和38周时胎儿GFR预测值的中位数分别为0.47、1.2、2.5和4.9 ml/min(50% CV)。这些值与出生时立即观察到的新生儿值高度一致。推导得出的FUPR和肌酐函数可用于评估胎儿肾脏成熟度并预测胎儿肾脏清除率。