Maturation and growth of renal function: Dosing renally cleared drugs in children

Abstract

A model was developed that characterized the maturation and growth of the renal function parameters (RFPs) glomerular filtration rate (GF), active tubular secretion (AS), and renal plasma flow (Q_R). Published RFP values were obtained from 63 healthy children between the ages of 2 days and 12 years. Maturation over time was assumed to be exponential from an immature (RFP_im) to a mature (RFP_ma) level; for growth, RFP_im and RFP_ma were assumed to follow the allometric equation: RFP(age, W)=aW^be^{−kmat *}age+cW^b(1−e^{−kmat *}age), where W is body weight, k_mat is the maturation rate constant, b is the body weight exponent, and a and c are RFP_im and RFP_ma at unit W. The model-based equation was fitted to the age-W, RFP values by a nonlinear least-squares method. For GF, the maturation half-life was 7.9 months (90% maturation, 26 months), the body weight exponent was 0.662, and the ratio c/a (which reflected the magnitude of the maturation influence) was 3.1. For AS and Q_R, the maturation half-lives were about 3.8 months and the ratio c/a was about 1.8. For renally eliminated drugs, the model can be used to estimate dosing regimens that are based on the adult dosing regimen and the age and weight of the child.