Absorption, Metabolism, and Excretion of [¹⁴C]-Tolebrutinib After Oral Administration in Humans, Contribution of the Metabolites to Pharmacological Activity.

ABSTRACT:

Background and objective

Tolebrutinib is a covalent inhibitor of Bruton's tyrosine kinase, an enzyme expressed in B lymphocytes and myeloid cells including microglia, which are thought to be major drivers of inflammation in multiple sclerosis. This excretion balance and metabolism study evaluated the metabolite profile of tolebrutinib in healthy male volunteers.

Methods

Six healthy volunteers received a 60-mg oral dose of [¹⁴C]-tolebrutinib, and metabolite profiling of ¹⁴C-labeled metabolites was performed using a combination of liquid chromatography, mass spectrometry, and radioactivity assay methods.

Results

Tolebrutinib was rapidly and completely absorbed from the gastrointestinal tract, followed by rapid and extensive metabolism. Excretion vi

SUBMITTER: Nicolas O 

PROVIDER: S-EPMC10480245 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature