COMPARISON OF PHARMACOKINETIC BEHAVIORS OF TWO HUMAN INTERFERONS (Lb-IFN-a AND Re-IFN-aA) IN CYNOMOLGUS MONKEYS BY 2'-5' OLIGOADENYLATE SYNTHETASE ASSAY

Abstract

Two human interferons (IFNs), natural lymphoblastoid IFN-α (Lb-IFN-α) and recombinant IFN-α (Re-IFN-αA) were compared for their induction of 2'-5' oligoadenylate (2-5A) synthetase and pharmacokinetic behaviors in cynomolgus monkeys. In in vitro experiments, (1) the enzyme activity induced in an epithelial cell strain from human amniotic membrane (FL) cells was much higher than that in primary culture of cynomolgus monkey kidney (PMK) cells, and (2) Lb-IFN-α induced higher levels of the enzyme than did Re-IFN-αA in both cells. In in vivo experiments, (1) no difference was found in clearance from the blood between the two IFNs, but the half life of the enzyme induced in peripheral leukocytes by Lb-IFN-α was about twice longer than that by Re-IFN-αA, and (2) the enzyme levels detected in various tissues were IFN-dose dependent. These results indicate that natural Lb-IFN-α is more effective in inducing 2-5A synthetase than Re-IFN-αA, and that the enzyme activity of various tissues as well as peripheral blood lymphocytes (PBL) increased in the cynomolgus monkeys administered with human IFNs.