Physiologically Based Pharmacokinetic Models for Infliximab, Ipilimumab, and Nivolumab Developed with GastroPlus to Predict Hepatic Concentrations.

ABSTRACT: Background/Objectives: Infliximab, ipilimumab, and nivolumab are three monoclonal antibodies that have been associated with hepatotoxicity. Three separate physiologically based pharmacokinetic (PBPK) models were developed in GastroPlus^® to simulate plasma and liver concentrations in patient populations after administration of either infliximab, ipilimumab, or nivolumab. Methods: The models include distribution and clearance mechanisms specific to large molecules, FcRn binding dynamics, and target-mediated drug disposition (TNF-α for infliximab, CTLA-4 for ipilimumab, and PD-1 for nivolumab). Results: The PBPK model for each large molecule was able to reproduce observed plasma concentration data in patient populations, including patients with rheumatoid arthr

SUBMITTER: Vallejo C 

PROVIDER: S-EPMC11945841 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature