The lymphatic route--III. Pharmacokinetics of human natural interferon-beta injected with albumin as a retarder in rabbits

Abstract

The aim of the present investigation was to define whether multisite, subcutaneous (s.c.) administration in unanesthetized, unrestrained rabbits of human natural interferon-beta (nat. IFN-beta) either in saline, or in a human albumin (ALB) solution (10 and 13% final concentrations) modified the pharmacokinetic parameters calculated from the IFN plasma levels. Plasma disappearance rates of nat. INF-beta were measured in two rabbits after intravenous (i.v.) administration and the kinetic was adequately represented by a bi-exponential curve. The highest ALB concentration (13%) caused a significant reduction of the plasma IFN Cmax, a longer half-life, a three-fold increase of the area under curve (AUC value) and a marked decrease of the plasma clearance. Interestingly, the bio-availability of IFN was increased almost four-fold. The data suggest that, when nat. IFN-beta is injected subcutaneously, the presence of a high concentration of ALB may prevent its inactivation and may favour its absorption via lymphatics rather than blood capillaries. It is remarkable that by using this approach, low but constant IFN levels are maintained for as long as two days, a fact that may well increase the therapeutic index of IFN in patients.