Different pharmacokinetics between natural and recombinant human interferon beta in rabbits

The pharmacokinetic behavior of recombinant (r) HuIFN-beta was compared with that of fibroblast-derived HuIFN-beta 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 (beta, Kel or K10) were almost the same in both IFNs, there were significant differences for the parameters (alpha, K12, K21, V1, V2, Vdss) 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-beta 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-beta was higher than that of fibroblast-derived HuIFN-beta. These results suggest that the deficiency of carbohydrate moiety conjugated with IFN molecule may influence the distribution property in vivo.