Pharmacokinetics/pharmacodynamics

Two RCTs compared higher-dose (20, 10, 10 mg/kg/day) versus lower dose (10, 5, 5 mg/kg/day) ibuprofen for treatment of PDA in extremely preterm infants with an increase in ductal closure rate reported. There was no difference in side effects. Peak concentrations were 109.8 (SD 27.2) micromol/L [24,25]. A pharmacokinetic study has shown drug elimination increases with postnatal age and recommended ibuprofen course: 10, 5, 5 mg/kg for neonates younger than 70 hours; 14, 7, 7 mg/kg between 70−108 hours; and 18, 9, 9 mg/kg between 108−180 hours. [26]

Ibuprofen is well absorbed orally. After a single dose of 10 mg/kg oral ibuprofen, levels were detectable 1 hour after administration, peaked after 8 hours and remained in a relative plateau until 24 hours post administration. Area under the curve 0 to 24 hours was higher than levels reported with intravenous treatment. [27]

The trough ibuprofen level >5 mg/L (25 µmol/L) after day 1 of treatment (10 mg/kg) was predictive of ductal close in a small case series. [28]

Amikacin clearance was reduced by 21% and vancomycin by 18% during co-administration of ibuprofen. The impact of indomethacin on vancomycin clearance was significantly higher compared to ibuprofen (46 and 28%, respectively). [29]