Pharmacokinetics of human recombinant interferon-beta in monkeys and rabbits

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 intravenous or intramuscular injection. After intravenous injection of 10(6) 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 pharmacokinetic 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 (10(7) units/kg) was injected intramuscularly into monkeys or rabbits, it remained detectable in the serum for 24 hr; an absorption phase and an elimination phase were seen. However, AUC (the area under the serum concentration curve) after the intramuscular injection of ReIFN -beta was about one-half and one-third of that after the intravenous injection in monkeys and rabbits, respectively. ReIFN -beta and IFN-beta (10(6) units/kg) were both detectable in the serum after intramuscular injection into rabbits, but the level of ReIFN -beta was lower than that of IFN-beta. These results indicate that the lack of carbohydrate in ReIFN -beta did not essentially affect the in vivo pharmacokinetics in monkeys and rabbits after intravenous injection, but this was not the case after intramuscular injection.