Oclacitinib is a Janus kinase (JAK) inhibitor. It can inhibit the function of a variety of cytokines dependent on JAK enzyme activity. For oclacitinib, the target cytokines are those that are proinflammatory or have a role in allergic responses/pruritis. However, oclacitinib may also exert effects on other cytokines (for example, those involved in host defence or haematopoiesis) with the potential for unwanted effects.

Following oral administration in dogs at a dose ranging from 0.55 to 0.9 mg oclacitinib/kg bodyweight, the observed mean Cmax was 352 ng/ml (ranging from 207 to 860 ng/ml), which occurred at approximately 1.7 hours (tmax) post dosing. The half-life (t1/2) is 4.8 hours in plasma.

Total body oclacitinib clearance from plasma was low – 316 ml/h/kg bodyweight (5.3 ml/min/kg bodyweight), and the apparent volume of distribution at steady-state was 942 ml/kg bodyweight. Oclacitinib exhibits low protein binding with 66.3% to 69.7% bound in fortified canine plasma at nominal concentrations ranging from 10 to 1,000 ng/ml.

Oclacitinib is metabolised in the dog to multiple metabolites. One major oxidative metabolite was identified in plasma and urine.

Overall, the major clearance route is metabolism, with minor contributions from renal and biliary elimination. Inhibition of canine cytochrome P450s is minimal, with IC50s 60-fold greater than the observed mean Cmax (281 ng/ml or 0.833 μM) following 0.6 mg/kg bw oral administration in the target animal safety study. Therefore, the risk of metabolic drug-drug interactions due to oclacitinib inhibition is very low.