Pharmacokinetics of Recombinant Leukocyte A Interferon Following Various Routes and Modes of Administration to the Dog

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Abstract
The pharmacokinetics of recombinant leukocyte A interferon (rIFN-αA) were studied following intravenous (i.v.) bolus, 60 min (i.v. inf.) infusion, intramuscular (i.m.), subcutaneous (s.c), and oral (p.o.) administrations to 15 male beagle dogs. Each animal received at least one 3 × 106 units/kg dose of rIFN-αA by one of the five routes and/or modes of administration. Blood samples were collected and the serum was separated and analyzed for rIFN-αA concentrations by an enzyme immunoassay, ELISA. There were no measurable rIFN-αA concentrations (< 0.020 ng/ml) following oral administration. In general serum rIFN-αA concentrations exceeded 100 ng/ml following i.v. bolus and infusion doses then declined rapidly in a biphasic manner. The volume of distribution at steady state Vdss ranged from 0.14 to 0.21 liters/kg after i.v. infusion. Total body serum clearance (ClB) ranged from 14.6 to 23.9 ml/min, which is about 50% the estimated inulin clearance in dogs. The harmonic mean elimination half-lives ranged from 4.5 to 9.5 h. A prolonged absorption profile was seen following i.m. and s.c. administrations and the systemic bioavailability for both routes was 42% when compared with the i.v. infusion. These appear to be the first pharmacokinetic profiles of rIFN-αA reported in the dog.