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. 2021 Jan 25:11:610294.
doi: 10.3389/fphar.2020.610294. eCollection 2020.

Creatinine Trends to Detect Ibuprofen-Related Maturational Adverse Drug Events in Neonatal Life: A Simulation Study for the ELBW Newborn

Tamara van Donge  1 , Karel Allegaert  2   3   4 , Marc Pfister  1 , Anne Smits  2   5 , John van den Anker  1   6   7
Affiliations

Creatinine Trends to Detect Ibuprofen-Related Maturational Adverse Drug Events in Neonatal Life: A Simulation Study for the ELBW Newborn

Tamara van Donge et al. Front Pharmacol. .

Abstract

Background: Recognizing a change in serum creatinine concentrations is useful to detect a renal adverse drug reaction signal. Assessing and characterizing the nephrotoxic side-effects of drugs in extremely low birth weight (ELBW, ≤1000 g) neonates remain challenging due to the high variability in creatinine in this population. This study aims to investigate and quantify the impact of ibuprofen treatment on kidney function, reflected by serum creatinine. Method: A recently developed dynamical model for serum creatinine was used to simulate creatinine profiles for typical, reference ELBW neonates with varying gestational and postnatal ages whilst being exposed to ibuprofen treatment. Results: The increase of serum creatinine concentrations due to ibuprofen treatment is most apparent during the first week of life. The difference in serum creatinine values between ibuprofen-exposed vs. non-exposed neonates decreases with increasing postnatal age, independent of gestational age. Conclusion: The difference in serum creatinine concentrations between ibuprofen-exposed vs. non-exposed neonates decreases with postnatal age, indicating an increased clearing capacity and resulting in a weak ibuprofen-related adverse drug reaction signal beyond early neonatal life.

Keywords: ELBW neonates; creatinine clearance; ibuprofen; nephrotoxicity; serum creatinine.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Predicted serum creatinine concentration-time profiles for four typical reference GA ELBW neonates: dotted lines represent serum creatinine concentration under ibuprofen treatment; solid line represents the absence of ibuprofen treatment. GA, gestational age; ELBW, extremely low birth weight.
FIGURE 2
FIGURE 2
Predicted creatinine clearance profiles for four typical reference GA ELBW neonates: dotted lines represent creatinine clearance under ibuprofen treatment; solid line represents the absence of ibuprofen treatment. GA, gestational age; ELBW, extremely low birth weight.
See this image and copyright information in PMC

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