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

Clinical Pharmacology and Therapeutics
Yifei ZhangJian Wang

Abstract

The estimated glomerular filtration rate (eGFR) equations based on serum creatinine (SCR) have been used for pediatric dose adjustment in drug labeling. This study evaluated the performance of those equations in estimating individual clearance of drugs that are predominantly eliminated by glomerular filtration, using clinical data from the renally eliminated drugs gadobutrol, gadoterate, amikacin, and vancomycin. The eGFR was compared with the observed drug clearance (CL) in 352 pediatric patients from birth to 12 years of age. Multiple eGFR equations overestimated the drug CL on average, including the original and bedside Schwartz equations, which showed an average eGFR/CL ratio between 1 and 3. Further analysis with bedside Schwartz equation showed a higher eGFR/CL ratio in the subjects with a lower SCR or CL. Supraphysiological eGFR as high as 380 mL/min/1.73 m2 was obtained using the bedside Schwartz equation for some of the subjects, most of whom are children < 2 years of age with SCR < 0.2 mg/dL. Excluding the subjects with supraphysiological eGFR from the analysis did not change the overall trend of overestimation. In conclusion, Schwartz equations led to an overestimation of drug clearance for the drugs evaluated. When ...Continue Reading

References

Sep 5, 2008·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·George J SchwartzAlvaro Muñoz
Jan 23, 2009·Journal of the American Society of Nephrology : JASN·George J SchwartzSusan L Furth
Dec 17, 2009·Clinical Pharmacokinetics·Andrew A UdyJeffrey Lipman
Jan 4, 2013·PloS One·Vandrea Carla De SouzaLaurence Dubourg
Jun 14, 2016·Journal of Clinical Pharmacology·Shankar LankeCatherine M Sherwin
Feb 17, 2017·Journal of Clinical Laboratory Analysis·Tuncay KümeAli Rıza Sisman
Dec 13, 2017·Advances in Chronic Kidney Disease·Ayesa N Mian, George J Schwartz
Oct 10, 2018·Therapeutic Drug Monitoring·Xiaoxi LiuCatherine M T Sherwin
Feb 7, 2019·Pharmacotherapy·Aaron M Cook, Jimmi Hatton-Kolpek

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Citations

Mar 25, 2021·JAMA : the Journal of the American Medical Association·Kimberly Maxfield, Issam Zineh

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