Maturation and growth of renal function: Dosing renally cleared drugs in children
Journal Title: The AAPS Journal - Year 2000, Vol 2, Issue 1
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 (QR). 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 (RFPim) to a mature (RFPma) level; for growth, RFPim and RFPma were assumed to follow the allometric equation: RFP(age, W)=aWbe−kmat*age+cWb(1−e−kmat*age), where W is body weight, kmat is the maturation rate constant, b is the body weight exponent, and a and c are RFPim and RFPma 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 QR, 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.
Authors and Affiliations
William L. Hayton
Keywords
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- DOI 10.1208/ps020103
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