Creatinine-Based Renal Function Assessment in Pediatric Drug Development: An Analysis Using Clinical Data for Renally...

Area of Science:

• Pediatric Nephrology
• Pharmacokinetics
• Drug Dosing

Background:

• Estimated glomerular filtration rate (eGFR) equations using serum creatinine (SCR) are standard for pediatric drug dose adjustment.
• Accurate eGFR is crucial for optimizing drug efficacy and safety in children.

Purpose of the Study:

• To evaluate the performance of common eGFR equations in estimating drug clearance in pediatric patients.
• To assess the accuracy of eGFR in predicting the clearance of renally eliminated drugs.

Main Methods:

• Compared eGFR from multiple equations against observed drug clearance (CL) in 352 pediatric patients (birth to 12 years).
• Utilized clinical data for renally eliminated drugs: gadobutrol, gadoterate, amikacin, and vancomycin.
• Analyzed eGFR/CL ratios, focusing on variations related to SCR and CL levels.

Main Results:

• Multiple eGFR equations, including Schwartz equations, consistently overestimated drug CL (average eGFR/CL ratio 1-3).
• The bedside Schwartz equation showed higher overestimation in subjects with lower SCR or CL.
• Supraphysiological eGFR values (up to 380 mL/min/1.73 m²) were calculated for young children (<2 years) with very low SCR (<0.2 mg/dL).

Conclusions:

• Schwartz equations lead to significant overestimation of drug clearance in pediatric patients.
• Current eGFR equations may not provide sufficient precision for pediatric drug dosing.
• Revised Schwartz equation constants or novel GFR estimation methods are recommended for improved accuracy.