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

• Tác giả: Karel Allegaert, Michael Garle, Robin Michelet, Olusola Olafuyi
• Ngôn ngữ: eng
• Ký hiệu phân loại: 612.665 Climacteric
• Thông tin xuất bản: England : Journal of clinical pharmacology , 2025
• Bộ sưu tập: NCBI
• ID: 677623

Tóm tắt

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