• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Scientific Publications by FDA Staff

  • Print
  • Share
  • E-mail

Search Publications



Starting Date

Ending Date

Order by

Entry Details

Clin Pharmacol Ther 2020 Jul 22 [Epub ahead of print]

Creatinine-based renal function assessment in pediatric drug development: an analysis using clinical data for renally eliminated drugs.

Zhang Y, Sherwin CM, Gonzalez D, Zhang Q, Khurana M, Fisher J, Burckart GJ, Wang Y, Yao LP, Ganley CJ, Wang J


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 clearance 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/1.73m(2) was obtained using bedside Schwartz equation for some of the subjects, most of whom are children less than two 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 greater precision is required in predicting eGFR for pediatric patients, such as in drug dosing, revised k constants for the Schwartz equation or new methods of GFR estimation may be necessary.

Category: Journal Article
PubMed ID: #32696977 DOI: 10.1002/cpt.1991
Includes FDA Authors from Scientific Area(s): Drugs Toxicological Research
Entry Created: 2020-07-26