Modification of TNF-alpha pharmacokinetics in SA-1 tumor-bearing mice.

Fibrosarcoma-SA-I-tumor-bearing mice were treated s.c. in the vicinity of tumors (peri-tumorally) or intravenously, with recombinant human TNF-alpha lacking 1 to 3 amino acids from N-terminal part (TNF-alpha Nv3). Tumor growth delay, observed after both routes of TNF-alpha Nv3 application, was statistically significant, though a better anti-tumor effect was achieved after peri-tumoral application. TNF-alpha Nv3 serum levels were determined in these animals and compared with TNF-alpha Nv3 serum levels in healthy animals, which were treated with TNF-alpha Nv3 either s.c. or i.v. The peak serum levels of TNF-alpha Nv3 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-alpha Nv3 elimination from the serum of tumor-bearing mice was slower than that in healthy animals. Also, comparison of TNF-alpha Nv3 pharmacokinetic parameters for tumor-free and sarcoma- or melanoma-bearing mice has demonstrated that the pharmacokinetics of TNF-alpha Nv3 are modified in tumor-bearing animals.