FIGURE 9.

In vivo pharmacokinetic and pharmacodynamic profile for PRN694 and in vivo inhibition of delayed type hypersensitivity in mice. A, thymocytes were harvested from mice at the indicated time points following intraperitoneal administration of 20 mg/kg PRN694. The thymocytes were treated with an irreversible fluorescent probe for ITK to measure the target occupancy. After separation by SDS-PAGE, the amount of probe binding was measured by fluorescence scanning of the gel. Plasma was also harvested, and the concentration of PRN694 in the plasma was determined by mass spectrometry. B, mice were sensitized with oxazolone on the shaved abdomen and then 7 days later were challenged with oxazolone on both sides of the right ear or vehicle on both sides of the left ear. One hour prior to the challenges, mice were dosed intraperitoneally with vehicle, 0.5 mg/kg dexamethasone (positive control), or PRN694 (20 mg/kg). Twenty-four hours after the challenge, ear edema was measured by weighing 7-mm ear cores. *, p < 0.05. Error bars, S.E.