Article Text
Abstract
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+6 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 (AUC0–72h >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 AUC0–72h 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 (AUC0–72h >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.
- neonatology
- pharmacology
Data availability statement
Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. The datasets generated during and/or analysed during the current study are available from the corresponding author (ORCID identifier: https://orcid.org/0000-0001-8385-0657) on reasonable request.
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Data availability statement
Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. The datasets generated during and/or analysed during the current study are available from the corresponding author (ORCID identifier: https://orcid.org/0000-0001-8385-0657) on reasonable request.
Footnotes
SS-Z and TvD contributed equally.
CS and JVDA contributed equally.
Contributors SS-Z and JVDA conceptualised the study. SS-Z and AA designed the study. GJ and GF collected the data. GF established and validated the laboratory method. MJR contributed to the design of the study. TvD conducted the literature search and carried out the initial population pharmacokinetic (PK) analysis. TvD and CS performed statistical analyses. AA contributed to the statistical interpretation. SS-Z, CS, MP and JVDA provided relevant input that increased the quality of the manuscript substantially. TvD drafted the initial manuscript. Each author listed on the manuscript has seen and approved the submission of this version of the manuscript.
Funding SS-Z is supported by New Investigator Fund, Hamilton Health Sciences. TvD, MP, AA, CS and JVDA are supported by the Eckenstein-Geigy foundation.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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