Absorption, disposition and metabolic pathway of amiselimod (MT-1303) in healthy volunteers in a mass balance study. (2nd September 2019)

• Record Type: Journal Article
• Authors: Kifuji, Takayuki; Inoue, Shinsuke; Furukawa, Megumi; Perez Madera, Begonya; Goto, Takahiro; Kumagai, Hiroshi; Mair, Stuart J; Kawaguchi, Atsuhiro
• Is Part Of: Xenobiotica. Volume 49:Number 9(2019:Sep.)
• Page Start: 1033
• Page End: 1043
• Publication Date: 2019-09-02
• Subjects: Amiselimod -- autoimmune -- mass balance study -- multiple sclerosis -- pharmacokinetics -- phase I -- safety -- sphingosine-1-phosphate 1 receptor modulator -- tolerability; Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.1080/00498254.2018.1525508
• Languages: English
• ISSNs: 0049-8254

Abstract

Abstract: The absorption, metabolism and excretion of MT-1303 were investigated in healthy male subjects after a single oral dose of 0.4 mg [14C]-MT-1303 (ClinicalTrials.gov NCT02293967). The MT-1303 concentration in the plasma reached a maximum at 12 h after administration. Thereafter, the concentration declined with a half-life of 451 h. At the final assessment on Day 57, 91.16% of the administered radioactivity was excreted, and the cumulative excretion in the urine and faeces was 35.32% and 55.84%, respectively. The most abundant metabolite in plasma was MT-1303-P, which accounted for 42.6% of the area under the plasma concentration–time curve (AUC) of the total radioactivity. The major component excreted in urine was Human Urine (HU)4 (3066434), accounting for 28.1% of radioactivity in the sample (4.05% of the dose), whereas MT-1303 was a major component in the faeces, accounting for 89.8% of radioactivity in the sample (25.49% of the dose) up to 240 h after administration. This study indicates that multiple metabolic pathways are involved in the elimination of MT-1303 from the human body and the excretion of MT-1303 and MT-1303-P via the kidney is low. Therefore, MT-1303 is unlikely to cause conspicuous drug interactions or alter pharmacokinetics in patients with renal impairment. Trial registration: ClinicalTrials.gov identifier: NCT02293967.