Studies on tumor necrosis factor (TNF). III. Plasma disappearance curves after intramuscular, subcutaneous, intraperitoneal, and oral administration of human recombinant TNF.

Abstract

Since clinical trials with TNF as a therapeutic agent for cancer are in progress, in this study we have chosen to compare the metabolic characteristics of 125I-labeled and unlabeled RTNF after administration through IM, SC, IP and PO routes. Both RTNF and 125I-RTNF plasma concentration profiles showed an absorption phase and a biexponential decline common to all routes of administration. Moreover the pharmacokinetic analysis indicates that TNF blood levels following SC injection are rather similar to those seen after IM dose. No difference has been found in T max. In contrast, the Kel is apparently increased in the SC route, but the difference is not significant. While a prolonged absorption phase had been obtained after IP injection of RTNF, comparison of t 1/2 beta and Kel between IP and SC or IM route failed to reveal significant differences. Surprisingly some plasma TNF bioactivity has been detected following oral administration.