Stress-related reductions in white blood cells and lymphocytes; minimal thymus atrophy
“Stress- or dehydration-related changes in clinical chemistry, hematology (such as reduced white blood cells and lymphocytes), and histopathology (such as increased hypertrophy of adrenal cortex corresponding to increased adrenal weight as well as minimal thymus atrophy) were observed across nonclinical studies”
✓ VerifiedFDA multi-discipline review, p. 163Source ↗
Biodistribution & persistence
Wide distribution in rats to liver, kidney, skin and skeletal muscle
“Total radioactivity (parent and metabolites) is distributed widely after IV dosing of oliceridine in rats, with 14C-concentrations found in well-perfused (liver, kidney) and poorly-perfused (skin, skeletal muscle) tissues.”
✓ VerifiedFDA multi-discipline review, p. 700Source ↗
Modality-specific risk
Disproportionate human metabolite TRV0109662 not adequately qualified; embryo-fetal effects not characterized (MIST)
“Specifically, it is not clear that the disproportionate major human metabolite, TRV0109662, has been adequately qualified for safety, because the exposure data for this metabolite from rat intravenous toxicity studies could not be reproduced. As such, it is not clear that effects of TRV0109662 on embryofetal development have been adequately characterized by the existing studies.”
✓ VerifiedFDA multi-discipline review, p. 165Source ↗