Scientific Poster Spotlight: Understanding the Absorption, Metabolism, and Excretion of Masitinib in Healthy Male Subjects

At the International Society for the Study of Xenobiotics (ISSX) conference in September 2022, Quotient Sciences [1], AB Science [2], the Netherlands Organisation for Applied Scientific Research (TNO) [3], and Pharmaron-UK [4] presented a poster investigating the absorption, metabolism, and excretion of masitinib, an oral tyrosine-kinase inhibitor that targets mast cells and macrophages and is currently in development as a potential treatment for neurology, inflammatory diseases, oncology, and viral diseases.

The key objectives of the open-label, single-period, radiolabeled study were to assess mass balance recovery, determine routes and rates of elimination, and enable metabolite profiling and identification for masitinib.

Six healthy male volunteers received a single oral dose of 14C-masitinib in the fasted state. Blood, plasma, urine, and feces samples were collected until 168 hours post-dose and analyzed for total radioactivity (TRA) by accelerator mass spectrometry (AMS). Samples collected during the study were pooled across timepoints and subjects, and metabolite profiling and identification was performed using an ultra-performance liquid chromatography (UPLC) system coupled to a high-resolution accurate mass spectrometer (HRMS).

On average, 69% of the radioactive dose was recovered by the end of the sampling period, with the majority recovered in feces. The main metabolites were identified, and the study results led to a hypothesis that there may be covalent binding of some masitinib metabolites to plasma proteins.

Overall, this study provided valuable insights on the absorption, metabolism, and excretion of masitinib, which informed the drug development program and regulatory filings.

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Poster authors

1. Quotient Sciences: I Shaw, S Mair

2. AB Science: F Pitré, F Bellamy

3. TNO: W Vaes, R de Ligt

4. Pharmaron-UK: R Cooke

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