Decreased thymus weight and lymphoid cellularity in dogs
“pituitary gland (increased weight and hypertrophy of pituitary basophils of the pars distalis), thymus (decreased weight and decreased lymphoid cellularity), and gallbladder (bile sludge).”
✓ VerifiedFDA multi-discipline review, p. 43Source ↗
Biodistribution & persistence
Wide distribution, highest in liver, kidney, thyroid, pancreas, lacrimal and adrenal glands; low brain penetration
“Following single oral administration, 14C-sotorasib-derived radioactivity distributed widely to rat tissues especially the liver, kidney, thyroid, pancreas, exorbital lacrimal gland, intra-orbital lacrimal gland, and adrenal gland, but brain penetration appeared low.”
✓ VerifiedFDA multi-discipline review, p. 42Source ↗
Modality-specific risk
Renal tubular toxicity in rats via β-lyase bioactivation to a sulfur-containing metabolite
“Increases in cysteine S-conjugate β-lyase pathway metabolism in the rat kidney compared to human may make rats more susceptible to renal toxicity due to local formation of a putative sulfur-containing metabolite than humans.”