Lymphatic transport of recombinant human tumor necrosis factor in rats.
The lymphatic transport of recombinant human tumor necrosis factor (rHu-TNF) was investigated after its administration via various routes in anesthetized rats. After intravenous (i.v.) administration, the level of rHu-TNF in the lymph reached a peak at 2 h, and thereafter decreased exponentially in a pattern similar to that of the elimination from plasma. Intramuscular (i.m.) and subcutaneous (s.c.) administrations resulted in low levels of rHu-TNF both in the plasma and in the lymph. On the other hand, intraperitoneal (i.p.), intra-stomach wall (s.w.) and intra-gut wall (g.w.) administrations gave high lymph levels of rHu-TNF. After the s.w., g.w. and i.p. administrations, the ratios of rHu-TNF recovered from the thoracic duct to the cumulative amount estimated from the rHu-TNF concentration in plasma were about 25, 32 and 8 times higher than in the case of i.v. administration, respectively. These results suggest that the routes of local administration of rHu-TNF such as s.w., g.w. and i.p. may be highly effective for the treatment of lymphatic metastasis of cancer.
Kojima
K
K
Pharmaceutical Research Laboratories, Dainippon Pharmaceutical Co. Ltd., Osaka, Japan.
Takahashi
T
T
Nakanishi
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001693:Biological Transport, Active; D006801:Humans; D008196:Lymph / Q000378:metabolism; D008207:Lymphatic Metastasis; D008208:Lymphatic System / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha