Mechanistic models create a framework for the study of pharmacokinetic changes in infancy. Understanding these changes allows a target concentration approach to therapy and potential for reduced toxicity. The target concentration may be undefined because of a paucity of effect measures.
Quantifying the effect of kidney disease on glomerular filtration rate (GFR) is important when describing variability in the clearance of drugs eliminated by the kidney. We aimed to develop a continuous model for renal function (RF) from prematurity to adulthood based on consistent models for fat‐free mass (FFM), creatinine production rate (CPR), and GFR. A model for fractional FFM in premature neonates to adults was developed using pooled data from 4462 subjects and 2847 FFM observations. It was found that girls have an FFM higher than that predicted from adult women based on height, total body mass, and sex, and boys have an FFM lower than adult men until around the onset of puberty, when it approaches adult male values. Data from 108 subjects with measurements of serum creatinine (Scr) and GFR were used to construct a model for CPR. Creatinine clearance was predicted using a model for CPR (based on FFM, postmenstrual age, and sex) and Scr that avoids discontinuous predictions between neonates, children, and adults. Individual CPR may then be used with individual Scr to predict the estimated GFR (eGFR; eGFR = CPR/Scr). A previously published model for human GFR based on 1153 GFR observations in 923 subjects without known kidney disease was updated using the model for fractional FFM to predict individual size and age‐consistent values for the expected normal GFR (nGFR). Individual renal function was then calculated using RF = eGFR/nGFR.
In Volume 21, Issue 3 of Pediatric Anesthesia, two typographical errors were made in Equation 1:1. The expression for WT3 should use etaWTMAX3 (not etaWTMAX1). 2. The logical expression for WT4 should start with (PMA>TLAGWT4)*FFEMWTMAX. (The greater than sign (>) was missing in a formatting error). The corrected Equation 1 appears in its entirety below, and a control stream that explains how the equations were used is available online (Data S1).We apologize for the error.Reference 1 Sumpter AL, Holford NH. Predicting weight using postmenstrual age -neonates to adults.
Summary
Objectives: To describe the pattern and variability of body weight with postmenstrual age (PMA) using nonlinear mixed effect modeling and to create a single mathematical function that can be used from prematurity to adulthood.
Background: PMA has been shown to predict functional properties of humans such as glomerular filtration rate and drug clearance. Widely used growth charts use postnatal age to predict weight in an idealized population and are not available as a mathematical function.
Methods: We modeled 7164 body weight and PMA observations from a pooled database of 5031 premature neonates, infants, children, and adults. All subjects were participants in pharmacokinetic or renal function studies. PMA ranged from 23 weeks to 82 years. A mixed effect model was used to describe fixed (PMA, sex) and random between‐subject variability.
Results: A model based on the sum of three sigmoid hyperbolic and one exponential functions described the data. Females were typically 12% lighter in weight. Part of the between‐subject variability in weight decreased exponentially with a half‐life of 3.5 PMA years, while the remainder stayed a constant fraction of the weight asymptote for each of the four functions.
Conclusions: The change of weight with PMA and sex can be described with a simple equation. This is suitable for simulation of typical weight–age distributions and may be useful for evaluation of appropriate weight for age in children requiring medical treatment.
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