PHARMACOKINETICS AND ANTIVIRAL ACTIVITY OF RECOMBINANT HUMAN INTERFERON-BETA(SER17) IN AFRICAN-GREEN MONKEYS

The pharmacokinetics and antiviral activity of recombinant human interferon-beta(ser17) (Betaseron) were evaluated in African green monkeys. In one study, animals infected with simian varicella virus were administered Betaseron intravenously (i.v.), intramuscularly (i.m.), or subcutaneously (s.c.) at doses of 1 x 10(6) or 1 x 10(7) IU/kg twice daily for 10 days. In another study, infected animals received Betaseron s.c. at doses of 1 x 10(6) IU/kg twice daily, 2 x 10(6) IU/kg once daily, 4 x 10(6) IU/kg every other day, or 6 x 10(6) IU/kg every 3 days for 10 days. Following i.v. administration, mean clearance, steady-state volume of distribution, and terminal half-life values for Betaseron were 0.36 +/- 0.08 liters/hr . kg, 0.65 +/- 0.09 liters/kg, and 1.9 +/- 0.43 h, respectively. Although bioavailability following i.m. and s.c. administration was only 30-50%, antiviral activity, as measured by reduction in viremia and appearance of skin rash, was comparable for i.v., i.m., and s.c. administration of 1 x 10(6) IU/kg of Betaseron twice daily. With increasing dose (1 x 10(6) IU/kg to 1 x 10(7) IU/kg), both the area under the serum concentration-time curve (AUC) and antiviral activity of Betaseron tended to increase. When comparing various s.c. dosing regimens, there was significant accumulation of Betaseron in serum with repeated twice-daily dosing. However, no accumulation of Betaseron in serum was observed if the dosing interval was less frequent than once daily. Antiviral activity was greatest with twice-daily or once-daily s.c. administrations of Betaseron.