Pharmacokinetic profile of edaravone: a comparison between Japanese and Caucasian populations

Abstract

Background: Amyotrophic lateral sclerosis (ALS) affects persons of all races, and there continues to be a need for effective therapies to treat the disease.

Objective: To compare the pharmacokinetics (PK) of edaravone between Japanese and Caucasian populations. Methods: Data from five PK studies among Japanese and Caucasian healthy volunteers were pooled and evaluated. In population PK (PPK) modelling, compartment models and other models with linear elimination were evaluated for appropriateness. Covariate effects by race, sex, weight, and age were investigated to explain variability in PK parameters. Simulations of the final PPK model were performed using a virtual population based on ALS clinical trials. Results: The analysis included 86 subjects. A three-compartment model with Michaelis-Menten plus linear elimination was selected as the best fit model. Race was statistically detected as a covariate for the second peripheral volume of distribution (V2), indicating a 26% increase for Caucasian subjects compared to Japanese subjects. However, based on simulation of PPK model for a virtual ALS population, the small difference of V2 was associated with a difference of C_tau around 1 ng/mL after infusion, which was minimal compared to C_max of approximately 1000 ng/ml. Conclusion: The PPK analyses demonstrated no clinically relevant difference in the PK profiles of edaravone by race, sex, weight, or age.

Keywords:

• Amyotrophic lateral sclerosis
• pharmacokinetic
• edaravone

Declaration of interest

YN, SK, AK, and MS are employees of MTPC. KT is an employee of MTDA. JP is an employee of MTPC and MTDA. The authors take full responsibility for the content of and the decision to submit this manuscript but thank Teresa A. Oblak of Covance Market Access Services Inc. for providing research support, coordination assistance, and editorial contributions.

Mitsubishi Tanabe Pharmaceutical Corporation (MTPC) was responsible for oversight of the PPK analysis performed by Cognigen Corporation. Mitsubishi Tanabe Pharma Development America (MTDA) provided medical writing support for this article. The ALSFTD supplement, Edaravone (MCI-186) in Amyotrophic Lateral Sclerosis (ALS), was funded by Mitsubishi Tanabe Pharma America, Inc.