NAPPA (version 1.0)
Research type
Research Study
Full title
Neonatal and Paediatric Pharmacokinetics of Antimicrobials study
IRAS ID
115463
Contact name
Mike Sharland
Contact email
Sponsor organisation
St George's, University of London
Eudract number
2013-002366-40
Research summary
Research Summary
Penicillins are antibiotics commonly used to treat infections in babies and children. This antibiotic family includes amoxicillin, benzylpenicillin, and flucloxacillin.
Historically, the doses of the penicillins used in children and babies have generally been calculated from doses used in adults. The scaling-down process considered factors such as age and body weight.
Nowadays, specialist computer software can be used to understand how the body of a child handles the antibiotic dose given and then to work out what the best dose is. However, for the software to be specific to children, we must measure the level of antibiotic in the blood after a dose has been given, which involves a blood test.
With modern laboratory methods, these measurements can be made successfully on very small quantities of blood; this is called 'microanalysis'. Such small quantities of blood would usually be discarded.
The aim of NAPPA is to develop new models to improve our understanding of how children process ('metabolise') penicillins, to help us discover if we can improve the dosing regimens used for children in the future.
The study population will involve children who need a penicillin antibiotic as part of their normal NHS care, and who also need blood tests or intravenous access. Therefore the antibiotic study can be done without the need for any extra invasive procedures, and there will be no change to the medication therapy received by participants.
In addition, NAPPA will evaluate whether it is feasible to measure antibiotic levels on a tiny drop of blood put onto absorbent paper (“dried blood spot”). This allows the sample to be stored and tested later on. NAPPA will compare the level of the antibiotic using this method with the level measured in the usual way, to show if this is a reliable method that could be used routinely in the future.
Summary of results
The NAPPA study (Neonatal and Paediatric Pharmacokinetics of Antimicrobials) was organized by St George’s University of London.
NAPPA investigated several medicines from the penicillin family of antibiotics including amoxicillin, co-amoxiclav, benzylpenicillin, flucloxacillin and piperacillin/tazobactam.
The aim of the NAPPA study was to further understand how children and babies of different ages process these medicines (known technically as “pharmacokinetics”), by measuring the level of antibiotic medicine in the blood after the dose is given, which involves a blood test.
The study recruited babies, children and teenagers from 9 hospitals in England, who all needed one of these penicillin antibiotics as part of their normal NHS care, and who also needed either blood tests or intravenous access. Therefore the antibiotic levels could be measured without the need for any extra invasive procedures, and there was no change to the medication therapy received by participants.
We used a method called pharmacokinetic modelling to analyse the results. This approach helped us to understand the impact of different doses in children of different ages and the factors that contribute to differences in response to treatment.
The study results enabled us to compare the effect of different antibiotic doses recommended in the British National Formulary for Children (which provides the standard dosing guidance that is used in the UK) and by the World Health Organization. The final pharmacokinetic model helped to demonstrate whether the dose (amount) of medicine recommended meets the required target or whether there is room for improvement.
From the study results, we developed the largest combined paediatric penicillin pharmacokinetic model to date, and the first paediatric pharmacokinetic model of flucloxacillin when given by mouth (orally). The final results provided evidence to support the high dose regimens that are recommended in the British National Formulary for Children. The results also helped us to identify areas that need further research to help optimise penicillin dosing for children and babies.
The final study results have been published in the Journal of Antimicrobial Chemotherapy and are available open access at this link: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbSC57-2FbeI7keTO1joKk0v-2Bw6ETpecIzgC7yJu200OQelpLCKbqTLrv0pJAg6pYywow-3D-3DPTzj_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YIUBGUXzC-2FWSBdzRjeJ4tux4kSOUyq14KUbxiSaeO6YFcSrY7IrEPnQ0tf-2FWlHd9bn441mcfxtCJAkMdTU2nEVh6YBuxx3u2Aa2AfYmhPMaYQNAZ8ZBtdJtD4f16Ua7McKfdJmqXoiod-2B-2BvTnP6-2B7Kbuc4n1vVnrTmgVMZXVc5bMg-3D-3D&data=05%7C01%7Cdulwich.rec%40hra.nhs.uk%7C629e65b8ff794ca2083508dbf7df5497%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638376310793851498%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=cTjko3nZHlAmCC19lS%2FoZBZf7j%2BASjoPb52jHyEfRNE%3D&reserved=0
REC name
London - Dulwich Research Ethics Committee
REC reference
13/LO/0907
Date of REC Opinion
19 Jul 2013
REC opinion
Favourable Opinion