Pharmacokinetics of tumor necrosis factor alpha after intravenous administration in rats. Dose dependence and influence of tumor necrosis factor beta.
2, 10, 20, 100 and 500 micrograms/kg/0.5 h of recombinant human tumor necrosis factor alpha (TNF-alpha) were administered to rats by intravenous infusion over 30 min. At high doses (greater than 10 micrograms/kg/0.5 h) the plasma half-life (t1/2, about 0.5 h) of TNF-alpha was practically dose independent. In contrast at the lowest dose (2 micrograms/kg/0.5 h) the elimination of TNF-alpha was markedly faster: A plasma half-life of only 5-8 min was determined. However, when in addition to 2 micrograms/kg/0.5 h of TNF-alpha a high dose of recombinant human tumor necrosis factor beta (TNF-beta) was infused the plasma half-life was enhanced up to values at high doses (greater than 10 micrograms/kg/0.5 h). Thus at the lowest dose the speed of elimination of TNF-alpha was enhanced which could be prevented by TNF-beta.
Zahn
G
G
Department of Biochemistry, Biberach an der Riss Fed. Rep. of Germany.
Greischel
A
A
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007262:Infusions, Intravenous; D008233:Lymphotoxin-alpha / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000493:pharmacokinetics*
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha