J. Chiang et al., PHARMACOKINETICS AND ANTIVIRAL ACTIVITY OF RECOMBINANT HUMAN INTERFERON-BETA(SER17) IN AFRICAN-GREEN MONKEYS, Journal of interferon research, 13(2), 1993, pp. 111-120
The pharmacokinetics and antiviral activity of recombinant human inter
feron-beta(ser17) (Betaseron) were evaluated in African green monkeys.
In one study, animals infected with simian varicella virus were admin
istered Betaseron intravenously (i.v.), intramuscularly (i.m.), or sub
cutaneously (s.c.) at doses of 1 x 10(6) or 1 x 10(7) IU/kg twice dail
y 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 dail
y, 4 x 10(6) IU/kg every other day, or 6 x 10(6) IU/kg every 3 days fo
r 10 days. Following i.v. administration, mean clearance, steady-state
volume of distribution, and terminal half-life values for Betaseron w
ere 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 r
eduction 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 twic
e daily. With increasing dose (1 x 10(6) IU/kg to 1 x 10(7) IU/kg), bo
th the area under the serum concentration-time curve (AUC) and antivir
al 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 B
etaseron in serum was observed if the dosing interval was less frequen
t than once daily. Antiviral activity was greatest with twice-daily or
once-daily s.c. administrations of Betaseron.