Pharmacokinetics of Recombinant Murine Interferon-γ in Mice

Administration of interferon-gamma (IFN-gamma) provides a new approach to the treatment of tumors and viral and microbial infections. The aim of this study was to evaluate the pharmacokinetics of recombinant murine IFN-gamma (rMuIFN-gamma) in the mouse system as a model for future investigations of the therapeutical effect of IFN-gamma. After a bolus injection of 2 x 10(4) LU/mouse by the intravenous (i.v.) route, a biphasical elimination pattern of the antiviral activity from the serum was detected in female and male C57BL/6 and CBA/2 mice with a beta half-life time of 19-32 min. After intramuscular (i.m.) and subcutaneous (s.c.) injection of rIFN-gamma, antiviral activity in serum could be detected from 30 to 270 min after the bolus application. There was a plateau in the activity from 65 to 135 min after s.c. and from 84 to 143 min after i.m. injection. Both kinetics fit with a pharmacokinetic model of biphasical elimination with an entrance compartment.