Guinea pig sensitization: no reaction after epidermal challenge; contact dermatitis unlikely
“No difference between the test and the control group was seen after epidermal challenge application, which suggests that the drug may not produce contact dermatitis.”
✓ VerifiedFDA multi-discipline review, p. 64Source ↗
Biodistribution & persistence
Extensive distribution in rats; slight accumulation after repeat dosing, 2-fold (thyroid, skin) to 6-fold (brain)
“Drug distribution was extensive in rats with only a slight accumulation in most organs and tissues investigated after 10 daily oral doses of 1 mg/kg. The accumulation of radioactivity was between 2-fold (thyroid and skin) and 6-fold (brain)”
✓ VerifiedFDA multi-discipline review, p. 45Source ↗
Modality-specific risk
QT prolongation in dogs, likely mediated by the sulfone metabolite
“QTc interval effects in the dog correlated with peak sulfone metabolite concentrations and hence, it is likely that the sulfone metabolite may be playing a role in the observed QTc interval prolongation.”
✓ VerifiedFDA multi-discipline review, p. 37Source ↗