title: Uptake of adriamycin by sarcoma transplants in the rat kidney: effects of renal arterial vs systemic constant rate infusion and of combination with ricin.
abstract: The uptake of adriamycin (Adm) by normal tissues and by sarcomas transplanted to both kidneys in rats was studied at 10 min following constant rate infusion of Adm 5 mg/kg body wt into one renal artery, during 3 and 10 min. Since the selectively infused kidney extracted only about 20% of the total dose, the present model provides a direct comparison of systemic versus selective i.a. infusions in each individual. Tumor Adm uptake was about 6 times higher on the selectively infused side. Adm uptake by tumor and normal renal tissue was proportional to the concentration X time product of Adm in arterial blood, in spite of highly different blood peak concentrations at different infusion rates. Ten-minute systemic intravenous infusion of the Adm dose, with concurrent infusion of ricin, 3 micrograms/kg, into one renal artery tended to increase Adm uptake by the tumors on both sides. This indicates a systemic rather than a local effect of ricin: ricin reduced Adm uptake by red blood cells and normal solid tissues and thus resulted in a delayed Adm clearance from the total plasma volume. In contrast, the relationship between tumor uptake and the concentration X time product of Adm in plasma was not affected by ricin, explaining the increased tumor uptake.
mesh_terms: D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D007261:Infusions, Intra-Arterial; D007263:Infusions, Parenteral; D007680:Kidney Neoplasms / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012077:Renal Artery; D012276:Ricin / Q000008:administration & dosage / Q000494:pharmacology*; D012513:Sarcoma, Experimental / Q000378:metabolism*; D013997:Time Factors
chemical_list: D004317:Doxorubicin; D012276:Ricin