Background <p>⁵¹Cr-EDTA and ^{99 m}Tc-DTPA clearances are two reference methods of determining the glomerular filtration rate. The study aimed to compare these two radioisotopic clearance measurements using an original approach based on population pharmacokinetics in oncopediatrics.</p> Methods <p>Plasma concentrations of ⁵¹Cr-EDTA and ^{99 m}Tc-DTPA obtained from, respectively, 40 and 19 children treated with nephrotoxic chemotherapy were simultaneously analyzed while accounting for three covariates (i.e., serum creatinine, plasma cystatin C, body weight) previously described as being related to the pediatric glomerular filtration rate. A binary covariate “GFR measurement” (MES = 0 or 1, respectively, for ⁵¹Cr-EDTA or ^{99 m}Tc-DTPA) was added to the model.</p> Results <p>Analysis revealed a non-significant bias (± 95% CI) of − 0.9% ± 11.4% between the two measurements (with ^{99 m}Tc-DTPA clearance overestimated).</p> Conclusions <p>This result confirmed that both radioisotopic clearances are equivalent in pediatrics, as has been reported in the literature on adults based on intrapatient comparisons. The value of the population approach in comparing the pharmacokinetics of two different compounds is thus demonstrated.</p> Graphical Abstract <p></p>