The impact of ibuprofen or indomethacin on renal drug clearance in neonates

Introduction. Administration of ibuprofen or indomethacin in neonates is associated with a reduction of glomerular filtration, reflected in a reduction in the elimination of drugs dependent on renal function for clearance. However, the magnitude of these effects and potential differences between ibuprofen or indomethacin remain unclear. Methods. Observations collected in two population pharmacokinetic studies in preterm neonates investigating amikacin and vancomycin disposition were used to estimate i the impact of ibuprofen administration and ii the difference between ibuprofen and indomethacin on renal drug clearance. Results. Amikacin clearance was reduced by 21 and vancomcyin was reduced by 18 during co-administration of ibuprofen. In a vancomycin pooled pharmacokinetic study, it was documented that the impact of indomethacin was significantly higher compared to ibuprofen 46 and 28, respectively. Conclusions. Both ibuprofen and indomethacin have a quantifiable impact on renal drug clearance. Compared to ibuprofen, the impact of indomethacin is more pronounced. Population modelling with covariate analysis can be a tool to disentangle the impact of various covariates, including ibuprofen or indomethacin, on renal drug clearance.