Tamara van Donge

Chapter 8 158 0.2 0.3 0.4 0.5 1 7 14 21 28 35 42 Postnatal age (days) Creatinine clearance (ml/min) Ibuprofen treatment Yes No GA (weeks) 24 27 29 32 Figure 2: Predicted creatinine clearance profiles for four typical 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. Discussion This simulation study illustrated that the effect of ibuprofen treatment is most pronounced during the first week of life, independent of gestational age. This difference in serum creatinine concentrations decreases with postnatal age, illustrating the increased renal clearance capacity during the early weeks of life and simultaneous blunting of the ibuprofen-related adverse drug reaction signal. During the first days after birth many physiological, maturational and potential pathological processes occur. The increase in serum creatinine concentrations during the first days after birth are the phenotypic net result of limited clearance capacities, drug exposure, tubular reabsorption (due to leaky tubules), maternal creatinine transfer and/or neonatal comorbidities. It remains challenging to disentangle between these contributing components.