Search

ObjectiveExploration of a novel therapeutic drug monitoring (TDM) strategy to personalise use of ibuprofen for closure of patent ductus arteriosus (PDA) in preterm neonates.DesignProspective, single-centre, open-label, pharmacokinetics study in preterm neonates.SettingNeonatal intensive care unit at McMaster Children’s Hospital.PatientsNeonates with a gestational age ≤28+6 weeks treated with oral ibuprofen for closure of a PDA.MethodsPopulation pharmacokinetic parameters, concentration-time profiles and exposure metrics were obtained using pharmacometric modelling and simulation.Main outcome measureAssociation 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).ResultsTwenty-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.ConclusionWe 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.

Davies et al 1 have quantified the prevalence of neonatal withdrawal syndrome (NWS) and its trend in England between 1997 and 2011, and have compared these findings with similar cohort studies in the USA, Western Australia and Canada. Using national hospital administrative data, the authors came to the conclusion that (a) there is variability in the NWS prevalence between the different hospital trusts in England with a prevalence above the 97th centile (3 SD) in 7% of the trusts and that (b) the recorded rate of NWS remained high, but stable with a prevalence rate of 2.7/1000 live births (1997–2011). The extensive variability in prevalence between hospitals or trusts confirms the data from a comparable report that used the relative number of neonatal intensive care unit (NICU) admissions for NWS in a given NICU as an indicator (number of NWS/total number of NICU admissions). While the median number was 4%, a 20-fold variability, from less than 2% to more than 50% of admissions, was documented between units.2 Similarly, there is also variability in the prevalence and its trends between countries. As discussed by the authors, this prevalence remained stable in Western Australia, but increased in the USA and Canada in more recent years. To further illustrate both the prevalence and its trend in different regions, we have reproduced the data as published by Davies et al 1 in combination with other data retrieved from the literature in figure 1.3 This exercise also illustrates that the stable prevalence …

BackgroundNeonates in intensive care units (NICU) are highly vulnerable to medication errors. Studies indicate that junior doctors have a prescribing error rate of up to 10%. Prescription errors result in overdosing or underdosing and affect clinical outcomes. Advances in mobile technology have brought opportunities for creating bedside decision support tools, including smartphone applications (apps). Ownership of smartphones and tablets by medical professionals is 80% or higher. The most commonly used apps amongst medical trainees are drug prescription guidelines and calculators.ResultsNovel drug prescription app based on reference texts such as the British National Formulary for children (BNFc), neonatal formulary seventh edition (NNF7) and the Red Book of the American Academy of Pediatrics. This app permits neonatologists to easily access up-to-date dose information and quickly calculate individual dose based on a patient's characteristics (e.g. weight, age, serum creatinine value).ConclusionApps for smartphones and tablets can serve as bedside decision support tools in neonatology. Pharmacometric modeling can be built in such apps to leverage historical and current patient data, individualize dosing strategies, and further optimize treatment benefits for neonates. Furthermore such applications may facilitate standardization of drug prescriptions among the nine NICUs in Switzerland.

The interesting work of Zhao et al ,1 in the June issue of the journal, recommends the use of a patient-tailored dosing regimen in an attempt to optimise continuous-infusion vancomycin (CIV) therapy in the newborn population. Despite the increasing use of CIV therapy during the past 10 years in neonates and young infants, the data on pharmacokinetics and dosing regimen of this drug are significantly lacking. Zhao et al 1 chose to investigate the results of vancomycin therapeutic drug monitoring under three different regimens and to develop an optimised dosing model with the aim to decrease the number of off-target vancomycin …

Dr Allegaert and colleagues wrote an outstanding review of the literature regarding the use of paracetamol to induce patent ductus arteriosus (PDA) closure.1 However, their discussion of the significant safety and efficacy concerns and the need for additional data was limited. It is important for the readership of the journal to be provided with more detailed information before paracetamol therapy is incorporated into routine clinical practice. It has been recognised that persistence of PDA is associated with increased morbidity and mortality in preterm infants.1 Infants with a clinically relevant PDA are commonly treated with cyclooxygenase (COX) inhibitors such as indomethacin or ibuprofen, yet these agents are …

Editorial by Banner and pp 1311, 1312 Drugs are subject to licensing procedures to ensure their quality, efficacy, and safety, but many drugs used to treat children in hospital are either not licensed for use in children (“unlicensed”) or are prescribed outside the terms of the product licence (“off label”).1 Little is known about such prescribing in general practice, so we conducted a cohort study in primary care in the Netherlands to investigate the subject. We retrieved data from the integrated primary care information project, a longitudinal observational database containing information from computer based patient records of 150 general practitioners in the Netherlands. The system complies with European Union guidelines on the use of medical data for medical research and has been proved valid for pharmacoepidemiological research.2 Within the dynamic population of children (0-16 years) registered in 1998, …