Absorption, distribution, metabolism and excretion of londamocitinib after single‐dose inhaled, intravenous and oral administration in healthy participants
Camille Riff, Peter Bold, Maria Heijer, Ryan A. Bragg, Danielle Steele, Tina Jellesmark Jensen, Davinder P. S. Dosanjh, Sabrina I. Hanswijk‐Bartelds, Esther van Duijn, Elwin R. Verheij, Somasekhara Menakuru, Rod Hughes, Helena DahlbäckAim
Methods
Pharmacokinetics, safety, metabolic profile and metabolite identification from plasma, urine, and faecal samples were assessed employing highly sensitive accelerator mass spectrometry. Participants received a single oral 4‐mg dose of [ 14 C]londamocitinib (NMT 37.0 kBq [ 14 C]) in Part 1 and an intravenous 30‐μg dose of [ 14 C]londamocitinib (NMT 37.0 kBq [ 14 C]), followed by a single inhaled dose of 3‐mg londamocitinib in Part 2.
Results
Mean recovery of total radioactive material after oral dosing was 76.3% in faeces and 8.7% in urine. After intravenous dosing, recovery was 67.3% in faeces and 16.0% in urine. Absolute bioavailability of oral londamocitinib was 40.4% and for inhaled administration was 62.5%. Unchanged londamocitinib constituted approximately 70% of circulating radioactivity in plasma and accounted for 47.8% and 28.4% of the administered dose in excreta after oral and intravenous administration respectively. No new safety signals were observed.
Conclusion
Following inhaled and oral dosing, londamocitinib demonstrated rapid absorption, and faecal excretion as the principal route of elimination. Unchanged londamocitinib and metabolite M6 were the major entities present in plasma, urine and faeces. Londamocitinib, at these doses, exhibited an acceptable safety and tolerability profile.