Preclinical pharmacokinetics and biodistribution of the dual adenosine A2A/A2B inhibitor muvadenant (M1069) in rats.

Muvadenant is a selective, dual A2A/A2B adenosine receptor antagonist that demonstrated anti-tumour efficacy in preclinical in vitro and in vivo models.In rats, 14C-muvadenant related radioactivity was quickly and widely distributed throughout the body with highest exposure observed in metabolic/excretory and melanin containing tissues and the gastrointestinal tract and lowest in the central nervous system.Following single oral administration, 6.27% of the radioactive dose was excreted via urine and 90.3% via faeces with a total recovery of 97.6%. After single intravenous dosing, the amounts of radioactivity excreted via urine and faeces were 13.7% and 80.2%, respectively, with a total recovery of 94.6% within 7 days.Whereas the parent compound accounted for the majority of the circulating radioactivity (>50%), metabolism plays the dominant role in the elimination of muvadenant.Metabolite structures derived from in vivo profiles in rats and in vitro incubations across species revealed extensive phase 1 metabolism of muvadenant with comparable metabolic pathways in human and preclinical species.