Exploring the Impact of Developmental Clearance Saturation on Propylene Glycol Exposure in Adults and Term Neonates Using Physiologically Based Pharmacokinetic Modeling.

ABSTRACT: Propylene glycol (PG) is a pharmaceutical excipient which is generally regarded as safe (GRAS), though clinical toxicity has been reported. PG toxicity has been attributed to accumulation due to saturation of the alcohol dehydrogenase (ADH)-mediated clearance pathway. This study aims to explore the impact of the saturation of ADH-mediated PG metabolism on its developmental clearance in adults and neonates and assess the impact of a range of doses on PG clearance saturation and toxicity. Physiologically based pharmacokinetic (PBPK) models for PG in adults and term neonates were developed using maximum velocity (V_max) and Michaelis-Menten's constant (K_m) of ADH-mediated metabolism determined in vitro in human liver cytosol, published physicochemical, drug-related and AD

SUBMITTER: Olafuyi O 

PROVIDER: S-EPMC11867916 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature