Effect of Dosing Schedule on Pharmacokinetics of Alpha Interferon and Anti-Alpha Interferon Neutralizing Antibody in Mice

Abstract

The influences of dosing time and dosing schedule on the plasma alpha interferon (IFN-α) concentration and the production of anti-IFN-α neutralizing antibodies were investigated in ICR male mice adapted to cycles of 12 h of light and 12 h of dark. In mice pretreated with IFN-α for 21 days, the plasma IFN-α concentrations were significantly lower than those in control mice (P < 0.01). The clearance of IFN-α and its volume of distribution obtained at steady state were significantly higher in the animals with IFN-α pretreatment than in the mice without IFN-α pretreatment. The area under the concentration-time curve and the mean residence time of IFN-α were significantly smaller in IFN-α-pretreated animals than in control animals. The plasma IFN-α levels (measured 2 h after dosing) were significantly lower in mice treated daily with IFN-α, while the anti-IFN-α neutralizing antibody levels (measured 24 h after dosing) were significantly increased on days 15 and 21 of treatment. Plasma IFN-α levels were significantly decreased in association with the production of anti-IFN-α neutralizing antibodies in mice treated with IFN-α daily at either 0900 or 2100 h. By contrast, the plasma IFN-α levels (measured 2 h after dosing) remained stable in mice treated with IFN-α at 0900 h on alternate days, while they were significantly lower after 21 days of treatment in mice treated with IFN-α at 2100 h on alternate days. These changes were associated with a significant increase in the levels of anti-IFN-α neutralizing antibodies in the latter group. The present findings suggest that an appropriate dosing schedule and/or dosing time for IFN-α may reduce the level of production of anti-IFN-α neutralizing antibodies in experimental and clinical situations

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“…The assay of recombinant proteins raises a specific problem, which is not faced with endogenous proteins. The administration of such recombinant proteins to animals and humans induces antibodies that may alter the elimination phase or sometimes reduce efficiency 17–20. These antibodies are present in the samples and may generate major interferences in the analytical method,21 and, more particularly in our assay, by competing with the antibodies adsorbed on protein G beads.…”

Pharmacokinetic studies of the recombinant chicken interferon-α in broiler chickens

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Interferon-alpha improves docetaxel antitumoral and antimetastatic efficiency in Lewis lung carcinoma bearing mice

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