Development of a PBPK Model for Lamotrigine which Incorporates Metabolism by UGT2B10: Impact of UGT2B10 Poor Metabolizer Phenotype and Pregnancy

• Published in: The AAPS journal Vol. 27; no. 1; p. 40
• Main Authors: Gardner, Iain, Heikkinen, Aki T., Tang, Lloyd Wei Tat, Lapham, Kimberly, Goosen, Theunis C.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 04.02.2025; Springer
• Subjects: Administration, Oral; Adult; Analysis; Anticonvulsants - administration & dosage; Anticonvulsants - pharmacokinetics; Area Under Curve; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Computer Simulation; Female; Genetic aspects; Glucuronosyltransferase - genetics; Glucuronosyltransferase - metabolism; Humans; Lamotrigine; Lamotrigine - administration & dosage; Lamotrigine - pharmacokinetics; Minor Histocompatibility Antigens - genetics; Minor Histocompatibility Antigens - metabolism; Models, Biological; Pharmacology/Toxicology; Pharmacy; Phenotype; Pregnancy; Pregnant women; Research Article; UGT2B10; PBPK; UGT1A4; lamotrigine
• ISSN: 1550-7416; 1550-7416
• DOI: 10.1208/s12248-025-01025-w

An updated physiologically based pharmacokinetic (PBPK) model was developed for lamotrigine by incorporating a component of metabolism due to a UDP-glucuronyltransferase (UGT) 2B isozyme. This was assigned to UGT2B10 based on recent in vitro data in our laboratory demonstrating metabolism of lamotri...