Novel strategy to personalise use of ibuprofen for closure of patent ductus arteriosus in preterm neonates.

OBJECTIVE

Exploration of a novel therapeutic drug monitoring (TDM) strategy to personalise use of ibuprofen for closure of patent ductus arteriosus (PDA) in preterm neonates.

DESIGN

Prospective, single-centre, open-label, pharmacokinetics study in preterm neonates.

SETTING

Neonatal intensive care unit at McMaster Children's Hospital.

PATIENTS

Neonates with a gestational age ≤28 weeks treated with oral ibuprofen for closure of a PDA.

METHODS

Population pharmacokinetic parameters, concentration-time profiles and exposure metrics were obtained using pharmacometric modelling and simulation.

MAIN OUTCOME MEASURE

Association between ibuprofen plasma concentrations measured at various sampling time points on the first day of treatment and attainment of the target exposure over the first 3 days of treatment (AUC >900 mg·hour/L).

RESULTS

Twenty-three preterm neonates (median birth weight 780 g and gestational age 25.9 weeks) were included, yielding 155 plasma ibuprofen plasma samples. Starting from 8 hours' postdose on the first day, a strong correlation between ibuprofen concentrations and AUC was observed. At 8 hours after the first dose, an ibuprofen concentration >20.5 mg/L was associated with a 90% probability of reaching the target exposure.

CONCLUSION

We designed a novel and practical TDM strategy and have shown that the chance of reaching the target exposure (AUC >900 mg·hour/L) can be predicted with a single sample collection on the first day of treatment. This newly acquired knowledge can be leveraged to personalise ibuprofen dosing regimens and improve the efficacy of ibuprofen use for pharmacological closure of a PDA.