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Maturation and growth of renal function: dosing renally cleared drugs in children
1Division of Pharmaceutics, College of Pharmacy, The Ohio State University, 500 West 12th Ave., Columbus, OH 43210-1291, USA. hayton.1@osu.edu
Insights
A new model quantifies renal function maturation in children, estimating glomerular filtration rate, active tubular secretion, and renal plasma flow. This model aids in adjusting pediatric drug dosages based on age and weight.
Area of Science:
- Pediatric Nephrology
- Pharmacokinetics
- Mathematical Modeling
Background:
- Renal function parameters (RFPs) like glomerular filtration rate (GF), active tubular secretion (AS), and renal plasma flow (QR) undergo significant maturation during childhood.
- Accurate characterization of these parameters is crucial for understanding drug disposition and optimizing pediatric dosing regimens.
Purpose of the Study:
- To develop and validate a mathematical model that describes the maturation and growth of key renal function parameters in healthy children.
- To provide a tool for estimating pediatric renal function based on age and body weight, facilitating accurate drug dosage calculations.
Main Methods:
- A model was developed using published RFP data from 63 healthy children aged 2 days to 12 years.
- The model assumes exponential maturation from immature to mature levels, incorporating allometric scaling with body weight.
- Nonlinear least-squares regression was employed to fit the model to age- and weight-specific RFP data.
Main Results:
- For GF, the maturation half-life was 7.9 months, with 90% maturation achieved at 26 months. The body weight exponent was 0.662, and the ratio of mature to immature function (c/a) was 3.1.
- For AS and QR, maturation half-lives were approximately 3.8 months, with a c/a ratio of about 1.8.
- The model successfully characterized the age- and weight-dependent changes in pediatric renal function.
Conclusions:
- The developed model provides a robust framework for understanding renal function maturation in children.
- This model can be utilized to estimate age- and weight-appropriate dosing regimens for renally eliminated drugs in pediatric populations.
- Accurate pharmacokinetic modeling based on maturation of renal function is essential for safe and effective pediatric pharmacotherapy.
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 (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(b)e(-kmat*age)+ cWb(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 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.