Clinical Pharmacology of Intravenous Paracetamol in Neonates

Effective analgesia in neonates is still hampered due to the lack of data on pharmacokinetics and –dynamics of analgesics in this specific population. To a certain extent, this is even true for paracetamol. An intravenous formulation might improve prediction of concentration and consequent effect compared to enteral administration. In this review, we summarize the consecutive steps reported in literature to document the pharmacokinetics, metabolism and hepatic tolerance of intravenous paracetamol in neonates. Based on a single intravenous dose study, pharmacokinetics estimates were calculated and a repeated dose regimen was developed. This dose regimen was subsequently evaluated in a repeated dose study, and paracetamol metabolism was described during repeated dose administration. Finally, hepatic tolerance in neonates was documented. Based on the available pharmacokinetic estimates, it seems that intravenous paracetamol is an attractive analgesic to be used in neonates, as an alternative or add-on therapy for opioid administration. After the documentation of the pharmacokinetics of paracetamol in neonates and in the absence of any data on pharmacodynamics of intravenous paracetamol in this population, prospective, well designed and appropriated powered pharmacodynamic studies in neonates are urgently