PHARMACOKINETIC PROPERTIES OF RECOMBINANT FELINE INTERFERON AND ITS STIMULATORY EFFECT ON 2', 5'-OLIGOADENYLATE SYNTHETASE-ACTIVITY IN THE CAT

The pharmacokinetic behavior of recombinant feline interferon produced in silkworm infected with recombinant baculovirus harboring cDNA coding for feline interferon was studied in vivo in cats. The decreasing profile of the serum interferon level after intravenous administration was fitted to a two-compartment model. The half-times of the first phase (distribution phase) and second phase (metabolic phase) were 5.0 +/- 0.5 min and 31 +/- 5 min, respectively. In the whole body autoradiogram, at 15 min after the administration, the highest radioactivity was observed in urine in the bladder, and predominant radioactivity in the kidneys, liver, thyroid gland and spleen. Almost no radioactivity was detected in the brain or fat. Three hr after administration, the highest radioactivity was recorded in the thyroid gland, urine in the bladder, intestinal contents, and gastric mucous membrane. The data obtained in this study suggest that recombinant feline interferon has similar pharmacokinetic properties to human interferons and that it is distributed primarily in the liver and kidneys, is catabolized rapidly mainly in the kidneys, and is excreted in the urine without residual accumulation in the body. It was confirmed that 2',5'-oligoadenylate synthetase activity was increased by the interferon in vivo for 3 days after an intravenous bolus injection in cats.