Tamara van Donge

Personalized use of ibuprofen in preterm neonates 105 6 0 1000 2000 3000 4000 0 10 20 30 40 50 ( R S ) − ibuprofen concentration at 8 h after first dose ( mg L ) AUC 0 − 72 at day 3 ( mg L × h ) Figure 2: AUC 0-72h versus (R/S)-ibuprofen concentration at 8 hours after start of treatment. Dotted line indicates target exposure of 900 mg·h/L. There is a strong correlation (R 2 >0.8) between AUC 0-72h and total (R/S)-ibuprofen concentrations with a high predictive performance (AUC-ROC >0.85) for reaching the target exposure when ibuprofen concentrations are measured at various sampling time points upward of 8 hours after the first ibuprofen dose (Table 2, Figure S3). Correlations and predictive performance increased with later sampling time points, being the highest for concentration minimum (C min ) (Table 2). When the ibuprofen concentration is measured 8 hours after the first dose, a concentration of at least 17.5 mg/L is necessary to reach 80% probability that the patient will reach the target exposure at day 3. When aiming for a 95% probability, the ibuprofen concentration should be at least 22.9 mg/L (Figure 3).