Pharmacokinetics of rhIL-15 assessed in rhesus macaques. (A) rhIL-15 pharmacokinetics were evaluated in rhesus macaques, with one set of animals receiving 12 infusions of 10 (•), 20 (■), and 50 (▴) μg/kg/d of rhIL-15 for 12 days, followed within 24 hours by killing and necropsy. IL-15 pharmacokinetics in this group were evaluated at 10, 30, 60 minutes, 4 hours, and 24 hours after the initial rhIL-15 administration. The mean terminal half-time was 1.11 ± 0.25 hours for the 10 μg/kg/d group, 1.10 ± 0.16 hours for the 20 μg/kg/d group, and 0.91 ± 0.11 hours for the 50 μg/kg/d group. (B) Other groups of animals each received the same doses and dosing schedule but were killed and necropsied at day 48 after a 36-day recovery period. In this set of animals, IL-15 pharmacokinetics were evaluated in the same schedule as in panel A after the 12th dose of rhIL-15. There was no statistical difference in the parameter values between day 1 (first infusion) and day 12 (final infusion) by Student t test, with the exception of the terminal slope of the 50 μg/kg/d animal. (C) A single additional animal received a 200 μg/kg/d dosage. At 24 hours after the IL-15 infusion, there was 270 pg/mL of rhIL-15 retained in this animal, a value only 0.04% of the ∼ 6 × 106 pg/mL at the 10-minute time point. Therefore, only in this latter animal was there any evidence for a prolonged persistence of rhIL-15 in the serum.
