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Published on: September 10, 2018
Renal drug clearance in preterm neonates: relation to prenatal growth
Karel Allegaert1, Brian J Anderson, John N van den Anker
1Department of Woman and Child, University of Leuven, Belgium. karel.allegaert@uz.kuleuven.ac.be
Insights
Preterm neonates born small for gestational age (SGA) exhibit reduced renal drug clearance, impacting aminoglycoside and glycopeptide elimination. This effect persists for the first four weeks of life, necessitating careful dosing adjustments.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Neonatal Physiology and Development
- Renal Function in Perinatal Life
Background:
- Aminoglycosides and glycopeptides are primarily cleared by the kidneys.
- Postmenstrual age (PMA) is a key factor in predicting drug clearance due to developing glomerular filtration rate (GFR).
- Intrauterine growth restriction (IUGR) impacts kidney development and function in neonates.
Purpose of the Study:
- To investigate the effect of prenatal growth, specifically small for gestational age (SGA) status, on the renal clearance of amikacin and vancomycin in preterm neonates.
- To determine if SGA influences drug clearance from birth up to four weeks of postnatal life.
Main Methods:
- Population pharmacokinetic analysis of 1212 drug measurements (vancomycin and amikacin) from 531 preterm neonates.
- Evaluation of various covariates, including size, PMA, and SGA status, on drug clearance.
- Comparison of drug clearance between neonates born small for gestational age (SGA) and appropriate for gestational age (AGA).
Main Results:
- Neonates born SGA demonstrated a significant 16.2% reduction in renal drug clearance compared to AGA controls.
- This reduced clearance in SGA neonates was observed from birth and persisted up to four weeks of postnatal age.
- While size and PMA were major predictors of clearance, SGA independently contributed to reduced drug elimination.
Conclusions:
- Renal drug clearance of aminoglycosides and glycopeptides is significantly lower in preterm neonates born SGA.
- The impact of SGA on drug clearance is evident early in postnatal life and warrants consideration in therapeutic drug monitoring.
- Prenatal growth status is an important factor influencing the pharmacokinetics of renally eliminated drugs in preterm infants.
Abstract:
Aminoglycosides and glycopeptides are almost exclusively eliminated by renal excretion. Postmenstrual age (PMA) is the best predictor of their clearance, presumably because it predicts the time course of development of the glomerular filtration rate (GFR). Intrauterine growth restriction has an impact on the normalized weight of the kidney, on the number of nephrons, on GFR, and on tubular function in human perinatal life. We investigated whether prenatal growth also affects clearance of drugs such as aminoglycosides or glycopeptides that are eliminated through the kidney. Observations collected in two population pharmacokinetic studies involving preterm neonates and investigating amikacin and vancomycin in the first month of postnatal life were used to estimate the impact of prenatal growth (as judged by birth weight for gestational age) on the clearance of these drugs. Data from 1212 drug measurements (vancomycin, 648; amikacin, 564) in 531 subjects (vancomycin, 249; amikacin, 282) were available for study. Neonates born small for gestational age (SGA) were found to have a 16.2% (coefficient of variation, 12.2%) reduction in drug clearance. This effect was present from birth up to the postnatal age of 4 weeks. The covariate size (weight 0.75) explained 47.3% of drug clearance; PMA, 25.2%; coadministration of a nonselective cyclo-oxygenase inhibitor, 3.5%; renal function, 7.6%; and SGA, 1.7%. Renal drug clearance is significantly lower in preterm neonates born SGA than in appropriate-for-gestational-age (AGA) controls. This reduced clearance was observed not only at birth but also up to the postnatal age of 4 weeks.
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