Development of a Population Pharmacokinetic Model for the Diroximel Fumarate Metabolites Monomethyl Fumarate and 2-Hydroxyethyl Succinimide Following Oral Administration of Diroximel Fumarate in Healthy Participants and Patients with Multiple Sclerosis.

ABSTRACT:

Introduction

Diroximel fumarate (DRF) is a next-generation oral fumarate that is indicated in the USA for relapsing forms of multiple sclerosis (MS). A joint population pharmacokinetic model was developed for the major active metabolite (monomethyl fumarate, MMF) and the major inactive metabolite (2-hydroxyethyl succinimide, HES) of DRF.

Methods

MMF and HES data were included from 341 healthy volunteers and 48 patients with MS across 11 phase I and III studies in which DRF was administered as single or multiple doses. Population modeling was performed with NONMEM version 7.3 with the first-order conditional estimation method.

Results

Estimated MMF clearance (CL_MMF), volume of distribution, and absorption rate constant (Ka) were 13.5 L/h, 30.4 L, and 5.04 h<

SUBMITTER: Kuchimanchi M 

PROVIDER: S-EPMC8857385 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature