The propylene glycol research project to illustrate the feasibility and difficulties to study toxicokinetics in neonates.

This paper aims to describe our propylene glycol (PG) research project to illustrate the feasibility and the difficulties encountered to perform excipient studies in neonates. PG is frequently co-administered excipient. PG accumulation potentially results in hyperosmolarity, lactic acidosis or hepato-renal toxicity in adults, reflecting issues related to pharmacokinetics (PKs) and -dynamics (PDs). Consequently, similar observations in neonates are urgently needed. Since newborns display 'physiological' impaired hepatic and renal elimination capacity, description of PG PK in neonates is warranted. The PG PD was assessed based on indicators of renal, hepatic and metabolic (in)tolerance earlier reported in adults and relating to osmolar changes. Based on the PK and PD data collected in neonates, we suggest that there is a lower limit of PG tolerance in neonates. In addition to preliminary data on PG disposition and tolerance in neonates, we mainly focus on the limitations of the current observations and the difficulties encountered during this PG project to further illustrate the specific setting of neonatal research.