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.
Kus
B
B
LEK Pharmaceutical and Chemical Company, d. d., Research and Development, Ljubljana, Slovenia.
Sersa
G
G
Novaković
S
S
Urbancic
J
J
Stalc
A
A
D000818:Animals; D001681:Biological Assay; D002461:Cell Line, Transformed; D004355:Drug Stability; D004797:Enzyme-Linked Immunosorbent Assay; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000378:metabolism; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D051379:Mice; D008805:Mice, Inbred A; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha