title: The pharmacokinetics of oclacitinib maleate, a Janus kinase inhibitor, in the dog.
abstract: The pharmacokinetics of oclacitinib maleate was evaluated in four separate studies. The absolute bioavailability study used a crossover design with 10 dogs. The effect of food on bioavailability was investigated in a crossover study with 18 dogs. The breed effect on pharmacokinetics was assessed in a crossover study in beagles and mongrels dogs. Dose proportionality and multiple dose pharmacokinetics were evaluated in a parallel design study with eight dogs per group. In all four studies, serial blood samples for plasma were collected. Oclacitinib maleate was rapidly and well absorbed following oral administration, with a time to peak plasma concentration of <1 h and an absolute bioavailability of 89%. The prandial state of dogs did not significantly affect the rate or extent of absorption of oclacitinib maleate when dosed orally, as demonstrated by the lack of significant differences in pharmacokinetic parameters between the oral fasted and oral fed treatment groups. The pharmacokinetics of oclacitinib in laboratory populations of beagles and mixed breed dogs also appeared similar. Following oral administration, the exposure of oclacitinib maleate increased dose proportionally from 0.6 to 3.0 mg/kg. Additionally, across the pharmacokinetic studies, there were no apparent differences in oclacitinib pharmacokinetics attributable to sex.
authors: Veterinary Medicine Research and Development, Zoetis, Kalamazoo, MI, USA.
authors: W T
authors: WT
authors: Collard
authors: B D
authors: BD
authors: Hummel
authors: A F
authors: AF
authors: Fielder
authors: V L
authors: VL
authors: King
authors: J F
authors: JF
authors: Boucher
authors: M A
authors: MA
authors: Mullins
authors: P B
authors: PB
authors: Malpas
authors: M R
authors: MR
authors: Stegemann
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004285:Dogs / Q000097:blood / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D008297:Male; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D003879:Dermatologic Agents; D011743:Pyrimidines; D013449:Sulfonamides; C588062:oclacitinib