Refined target-mediated drug disposition modeling of the anti-tissue factor pathway inhibitor antibody MG1113 in cynomolgus monkeys and rabbits.

ABSTRACT:

Introduction

MG1113 is a humanized immunoglobulin G4 antibody targeting the Kunitz-type protease inhibitor 2 domain of tissue factor pathway inhibitor (TFPI) and is under clinical investigation for hemophilia treatment. This study aimed to refine a previously developed target-mediated drug disposition (TMDD) model for MG1113 by incorporating both targets [e.g., soluble TFPI-α (sTFPI-α) and membrane-bound TFPI (mTFPI)] and a transit compartment to capture delayed absorption after subcutaneous (s.c.) dosing.

Methods

The refined TMDD model was fitted to the plasma profiles of MG1113 and sTFPI-α in cynomolgus monkeys that received various intravenous and s.c. doses of MG1113 using the Cluster Gauss-Newton Method (CGNM). The optimized model parameters were scaled allometrically a

SUBMITTER: Kwak H 

PROVIDER: S-EPMC12819659 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature