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Modification of TNF‐α pharmacokinetics in SA‐1 tumor‐bearing mice
Author(s) -
Kus Breda,
Serša Gregor,
Novaković Srdjan,
Urbančič Janja,
Štalc Anton
Publication year - 1993
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910550120
Subject(s) - fibrosarcoma , tumor necrosis factor alpha , pharmacokinetics , sarcoma , melanoma , recombinant dna , medicine , endocrinology , cancer research , pharmacology , chemistry , pathology , biochemistry , gene
Fibrosarcoma‐SA‐1‐tumor‐bearing mice were treated s.c. in the vicinity of tumors (peri‐tumorally) or intravenously, with recombinant human TNF‐α lacking 1to 3 amino acids from N‐terminal part (TNF‐αNv3). Tumor growth delay, observed after both routes of TNF‐αNv3 application, was statistically significant, though a better anti‐tumor effect was achieved after peri‐tumoral application. TNF‐αNv3 serum levels were determined in these animals and compared with TNF‐αNv3 serum levels in healthy animals, which were treated with TNF‐αNv3 either s.c. or i.v. The peak serum levels of TNF‐αNv3 applied peri‐tumorally/s.c. were significantly higher in tumor‐bearing than in healthy mice, whereas smaller differences in peak serum levels were found after i.v. application, which might correlate with anti‐tumor activity. Whatever the route of application, TNF‐αNv3 elimination from the serum of tumor‐bearing mice was slower than that in healthy animals. Also, comparison of TNF‐αNv3 pharmacokinetic parameters for tumor‐free and sarcoma‐ or melanoma‐bearing mice has demonstrated that the pharmacokinetics of TNF‐αNv3 are modified in tumor‐bearing animals. © 1993 Wiley‐Liss, Inc.