Revisiting drug dosing in neonates
Pharmacokinetic and pharmacodynamic studies on drugs prescribed to children are often inefficient. For medicines already on the market, companies have the opportunity to apply for a Paediatric Marketing Use Authorisation (PUMA). However, it is difficult to engage pharmaceutical industry to conduct paediatric research for off-patent drugs. This means that children receive either suboptimal or higher doses than necessary and exposing them to health risks. To fight neonatal bacterial blood infection (sepsis) and invasive candidiasis, the drugs ciprofloxacin and fluconazole are used, respectively. However, pharmacokinetic and safety data are missing for neonatal administration. The scope of the EU-funded project TINN (Evaluation of antibiotics (ciprofloxacin and fluconazole) for the treatment of infections in preterm and term neonates) was to fill the knowledge gap on dosing and safety of these two drugs. For this purpose, paediatric researchers from seven EU countries collaborated to conduct a paediatric investigation plan that commenced with pre-clinical studies. They used juvenile animals to examine the pharmacokinetics and toxicity of ciprofloxacin and fluconazole while in silico modelling approaches determined dosing. The next step involved randomised clinical trials on neonates to determine the pharmacokinetics, efficacy and safety of these two drugs against infection. Overall, the deliverables of the TINN study will ensure the prescription of appropriate and consistent doses for neonates in the EU. Long term this will translate towards a safe and efficacious administration of these anti-infective drugs in the vulnerable neonatal population.
Keywords
Neonates, pharmacokinetic, sepsis, candidiasis, ciprofloxacin, fluconazole, clinical trial
