Tamara van Donge

Chapter 6 106 10 12 14 16 18 20 22 24 8.0 10.0 12.0 14.0 16.0 18.0 20.0 23.5 Sampling time point after dose (h) Ibuprofen concentration to reach target AUC 0 − 72 Probability 80% 85% 90% 95% Figure 3: Nomogram illustrating the required (R/S)-ibuprofen concentrations associated with the target exposure (AUC 0-72h of 900 mg·h/L) versus various sampling time points after the first dose (h). Discussion In this study, we developed a single sampling strategy and demonstrated that the AUC 0- 72h can be predicted with a high probability using a single blood sample on day 1 of ibuprofen treatment. We have presented a nomogram that provides target concentrations for total (R/S)-ibuprofen measured at different sampling time points on the first day of treatment (Figure 3). With these findings, clinicians can identify patients with an increased risk of a subtherapeutic total ibuprofen AUC 0-72h and a potentially ineffective treatment at a very early stage. Application of serum concentrations to improve therapeutic efficacy, has been previously described for the use of intravenous indomethacin for closure of a PDA in preterm neonates. 20 To date, efforts to improve efficacy of pharmacological closure of PDA have mainly focused on the development of novel dosing regimens. 11,12,17 Although such an approach is valuable for improving success rates of ductal, it does not solve the issue of considerable variability in the resulting exposure due to the nature of the treated population. The proposed individualized approach is novel and marks an important first step in exploring different strategies to improve closure of PDA in preterm neonates. The specific TDM strategy for changing the dose amount and/or dosing interval in response to the observed concentration, needs to be carefully studied and validated