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Impact of Gestational Age and Birth Weight on Amikacin Clearance on Day 1 of Life

Michiel F. Schreuder^*, Abraham J. Wilhelm, Arend Bökenkamp^*, Simone M.H. Timmermans, Henriette A. Delemarre-van de Waal, and Joanna A.E. van Wijk^*

Departments of ^* Pediatric Nephrology, Pharmacy, Neonatology, and Pediatric Endocrinology, VU University Medical Center, Amsterdam, The Netherlands

Correspondence: Dr. Michiel F. Schreuder,Department of Pediatric Nephrology, 804, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Phone: +31-24-3666292; Fax: +31-24-3619348; E-mail: m.schreuder{at}cukz.umcn.nl

Background and objectives: Intrauterine growth restriction (IUGR) and prematurity are associated with a low nephron endowment. It can therefore be expected that neonates who are born premature and/or after IUGR have a lower GFR. Measurement of GFR in neonates is difficult, but the clearance of amikacin has been proven to be a reliable marker. We hypothesized that amikacin clearance is lower after IUGR or premature birth as a marker of low nephron endowment.

Design, setting, participants, & measurements: Amikacin clearance was retrospectively analyzed in 161 neonates who received amikacin within the first 24 h of life. Using the MW/Pharm computer program, a population one-compartment model was calculated. The mean population pharmacokinetic parameters were individualized for each patient according to the maximum a posteriori Bayesian fitting method and provided the amikacin clearance.

Results: Our results show that birth weight z score and gestational age are correlated with the clearance of amikacin (partial correlation coefficient 0.159, P = 0.046, and 0.396, P < 0.001, respectively), after correction for other factors.

Conclusions: We conclude that renal clearance on the first day of life is lower in neonates with a lower gestational age and/or birth weight z score. This indicates that both prematurity and IUGR impair GFR on the first day of life.