Different Pharmacokinetics Between Natural and Recombinant Human Interferon Beta in Rabbits

The pharmacokinetic behavior of recombinant (r) HuIFN-β was compared with that of fibroblast-derived HuIFN-β in rabbits using a pharmacokinetic model analysis with a computer curve-fitting. The observed data were in good agreement with a two-compartment open model in intravenous experiment, and with a one-compartment open model in intramuscular and continuous infusion experiments. Although the parameters of elimination phase (β, Kel or K₁₀) were almost the same in both IFNs, there were significant differences for the parameters (α, k₁₂, k_2i, V₁, V₂, Vd^ss) of distribution phase in intravenous experiment and for the parameter (Vd) of the steady-state level in continuous infusion experiment. These results indicate that rHuIFN-β has a larger distribution volume and a higher distribution rate from the central compartment to the peripheral. The serum levels in intramuscular experiment represented so-called flip-flop type of kinetics. Although the absorption rate from the injection site to the blood circulation was similar in both IFNs, the availability of rHuIFN-β was higher than that of fibroblast-derived HuIFN-β.

These results suggest that the deficiency of carbohydrate moiety conjugated with IFN molecule may influence the distribution property in vivo.