Prediction of total and renal clearance of renally secreted drugs in neonates and infants (≤3 months of age).

Background: Renal excretion is a major route of elimination for many drugs. Renal clearance is the sum of three processes: glomerular filtration, tubular secretion, and tubular re-absorption. Tubular secretion is an active transport process and is immature at birth. In the neonates, renal tubular secretion can be important for the elimination of those drugs which are renally secreted, such as penicillins and cephalosporins. Aim: The objective of this study was to evaluate the predictive performances of three models to predict total and renal clearance of renally secreted drugs in neonates (≤3 months of age). Methods: From the literature, clearance values for 12 renally secreted drugs for neonates and adults were obtained. Three models were used to predict the clearances of these drugs. The predictive performances of these models were evaluated by comparing the predicted values of total and renal clearance with the observed clearance values in the neonates. Results: There were 12 drugs with 22 observations (preterm and term neonates, ≤3 months of age) for total clearance and six drugs with eight observations for renal clearance. For both total and renal clearance, a prediction error of <50% was observed by all three models evaluated in this study. Conclusions: The proposed models can predict mean total and renal clearances of renally secreted drugs in preterm and term neonates (≤3 months of age) with reasonable accuracy (50% prediction error) and are of practical value during neonatal drug development. Relevance for Patients: The work may help in dose selection for neonates for medicines that are renally secreted.