Pharmacokinetics of Recombinant Alpha A Interferon Following IV Infusion and Bolus, IM, and PO Administrations to African Green Monkeys

The pharmacokinetics of recombinant alpha A interferon (rIFN- αA) were studied following an intravenous (iv) bolus, 60 min infusion, intramuscular (im), and oral administrations to four African Green monkeys. Each monkey received 3 x 106 units/kg of rIFN-αA parenterally and 6 x 106 units/kg orally. Blood samples were collected and the serum was separated and analyzed for rIFN-α-A concentrations by an enzyme immunoassay, ELISA. No significant changes in clinical chemistry values resulted from rIFN-αA administration. There were no measurable rIFN-αA concentrations (< 20 pg/ml) following oral administration. Serum rIFN-αA concentrations declined rapidly in a biphasic manner following iv bolus and infusion doses and were described by a single pharmacokinetic model. The volume of distribution at steady state (Vdss) ranged from 0.034 to 0.31 l/kg after iv infusion. Total clearance ranged from 4.5 to 19 ml/min, which is about 75% the estimated inulin clearance in monkeys, suggesting glomerular filtration without...