ERA-Net Priomedchild Call for proposals

Lead Research Organisation: University of Liverpool

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Technical Summary

Understanding the pharmacokinetics (PK) of drug metabolism in children is essential in determining therapeutic dosages and avoiding adverse events. However to obtain paediatric PK data particularly in the 0-2 year old age group is technically challenging. We therefore propose to develop and validate new approaches to obtain paediatric PK data in this age group using three model drugs viz. paracetamol, spironolactone and midazolam with the ultrasensitive bioanalytical technique, Accelerator Mass Spectrometry (AMS), which can measure parent drug and metabolite concentrations in very small volume blood samples.|AMS requires the administration of a microtracer of 14C-labelled drug and hence all the necessary ethical, legal, regulatory and scientific procedures will need to be developed to allow AMS studies in the paediatric population. Intensive blood sampling procedures will be used in a relatively few paediatric patients (up to 100 patients split across two paediatric clinics) to obtain high quality PK data; these data will be compared with literature PK data where sparse sampling procedures have been used.|Paediatric patients will be recruited in Tartu, Estonia, and Liverpool, UK. The PAMPERS model drugs will be given as part of normal clinical management; in order to facilitate recruitment, we will therefore recruit patients in environments which cause the least discomfort and do not lead to significant changes in clinical procedures, for example in the post-operative period or in the intensive care unit. 14C-Labelled certificated drugs will be provided by PRI, Poland and ethical and project management aspects by groups who have been previously involved in EU funded programmes. AMS bioanalysis will be performed at a new TNO AMS centre in Zeist, The Netherlands. The innovative procedures developed here will provide a better understanding of the utility of AMS to obtain paediatric PK data and could pave the way for AMS studies to be incorporated into Paediatric Investigation Plans. This would ultimately have the benefit of earlier introduction of new therapies to the paediatric population in|a safer, more effective and efficient manner with appropriate dosage regimes.

Publications

10 25 50
 
Description Addenbrookes hospital 
Organisation Addenbrooke's Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution Scientific discussion and decision-making for formulation and stability needs
Collaborator Contribution Formulation and release of 14-C labelled drugs for the clinical studies in the PAMPER project and production of stability data.
Impact Multi-discipline collaboration involving partners in the PAMPER consortium from Poland (chemists), Estonia (paediatric clinicians), UK (paediatric clinicians and bioanalysts)
Start Year 2012
 
Description GSK AMS Bioanalysis 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution Scientific discussions and proposals for accelerator mass spectrometry support
Collaborator Contribution Technical advice on sample preparation and analysis using accelerator mass spectrometry. Offer to analyse samples to aid PAMPER programme and ensure that it completes on time
Impact None yet
Start Year 2014