PHARMACOKINETICS OF HUMAN RECOMBINANT INTERFERON-BETA IN MONKEYS AND RABBITS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 75  (3) , 292-300
Abstract
The pharmacokinetics of human recombinant interferon-.beta. (ReIFN-.beta.) was compared with that of natural human interferon-.beta. (IFN-.beta.) in monkeys and rabbits after i.v. or i.m. injection. After i.v. injection of 106 units/kg of ReIFN-.beta. or IFN-.beta. into monkeys or rabbits, serum levels of both interferons declined biexponentially. No significant differences between ReIFN-.beta. and IFN-.beta. were detected in most pharamcokinetic parameters including T1/2-.beta., though T1/2-.alpha. of ReIFN-.beta. was significantly shorter than that of IFN-.beta.. These results seemed to be in conflict with the observed difference of stability of the interferons in vitro since ReIFN-.beta. was less stable than IFN-.beta. in monkey and rabbit serum. When ReIFN-.beta. (107 units/kg) was injected i.m. into monkeys or rabbits, it remained detectable in the serum from 24 h; an absorption phase and an elimination phase were seen. However, AUC (the area under the serum concentration curve) after the i.m. injection of ReIFN-.beta. was .apprx. 1/2 and 1/3 of that after the intravenous injection in monkeys and rabbits, respectively. ReIFN-.beta. and IFN-.beta. (106 units/kg) were both detectable in the serum after i.m. injection into rabbits, but the level of ReIFN-.beta. was lower than that of IFN-.beta.. The lack of carbohydrate in ReIFN-.beta. did not essentially affect the in vivo pharmacokinetics in monkeys and rabbits after i.v. injection, but this was not the case after i.m. injection. [Human interferons are presently undergoing clinical evaluations as therapeutic agents for virus infections and cancer.].