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Abstract Aims Whether and when glomerular filtration rate (GFR) in preterms catches up with term peers is unknown. This study aims to develop a GFR maturation model for (pre) term-born individuals from birth to 18 years of age. Secondarily, the function is applied to data of different renally excreted drugs. Methods We combined published inulin clearance values and serum creatinine (Scr) concentrations in (pre) term born individuals throughout childhood. Inulin clearance was assumed to be equal to GFR, and Scr to reflect creatinine synthesis rate/GFR. We developed a GFR function consisting of GFR birth (GFR at birth), and an Emax model dependent on PNA (with GFR max, PNA 50 (PNA at which half of GFR₌₀ₗ GFR max is reached) and Hill coefficient). The final GFR model was applied to predict gentamicin, tobramycin and vancomycin concentrations. Result In the GFR model, GFR birth varied with birthweight linearly while in the PNA-based Emax equation, GA was the best covariate for PNA 50, and current weight for GFR max. The final model showed that for a child born at 26 weeks GA, absolute GFR is 18%, 63%, 80%, 92% and 96% of the GFR of a child born at 40 weeks GA at 1 month, 6 months, 1 year, 3 years and 12 years, respectively. PopPK models with the GFR maturation equations predicted concentrations of renally cleared antibiotics across (pre) term-born neonates until 18 years well. Conclusions GFR of preterm individuals catches up with term peers at around three years of age, implying reduced dosages of renally cleared drugs should be considered below this age.
Wu et al. (Tue,) studied this question.
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