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.
Berlex Laboratories, Richmond, CA 94806.
J
J
Chiang
C A
CA
Gloff
K F
KF
Soike
G
G
Williams
D000818:Animals; D002644:Chickenpox / Q000188:drug therapy* / Q000378:metabolism; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008992:Monkey Diseases / Q000188:drug therapy* / Q000378:metabolism
D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a