Impact of ibuprofen administration on renal drug clearance in the first weeks of life

Abstract

The administration of ibuprofen or any other nonselective cyclooxygenase (COX) inhibitor drug in early neonatal life is associated with a reduction of glomerular filtration, which reduces the elimination of drugs dependent on renal function for clearance. However, the relationship between COX inhibitor drug indication (prophylactic or therapeutic) and the magnitude of this effect remains unclear. Observations collected in two population pharmacokinetic studies, in preterm neonates, investigating amikacin and vancomycin were used to estimate: i) the impact of ibuprofen administration on the clearance of these drugs; and ii) the difference between prophylactic and therapeutic administration of ibuprofen on this clearance. Prophylactic administration of ibuprofen to preterm neonates on the first day of life to enhance closure of an asymptomatic patent ductus arteriosus (PDA) reduced amikacin clearance by 21% while coadministration of ibuprofen to induce closure of a symptomatic PDA resulted in an 18% reduction in vancomycin clearance in the first month of postnatal life. A significant and clinically relevant reduction in drug clearance is observed when ibuprofen is coadministered independent of indication, postmenstrual or postnatal age. Population modeling with covariate analyses can provide us with the tools to further disentangle the impact of nonselective COX-inhibitors on renal drug clearance.