Clinical pharmacology of propylene glycol in neonates
Propylene glycol (PG) is an unintentional frequently co-administered solvent together with a therapeutic compound, despite the fact that PG accumulation potentially results in hyperosmolarity, lactic acidosis and renal/hepatic toxicity. By their nature, newborns are expected to have ‘physiological’ impaired hepatic and renal elimination capacity. Focused studies in neonates should enable us to unveil data on PG clearance and tolerance in this population. In consecutive steps, we documented PG disposition following iv administration of PG and renal PG elimination in neonates, and compared these findings with observations in adults. Finally, we documented aspects of tolerance of PG in neonates. The data on PG disposition and tolerance suggest that there is a lower limit of safe short term exposure to PG in neonates. Such a safer level of exposure should finally be based on clearance estimates and level of tolerated exposure. Besides the compound specific observations, we illustrated that it is feasible and possible to prospectively assess aspects of disposition and tolerance of solvents in neonates. Key-Words: formulation – propylene glycol – newborn – maturation – developmental toxicology