Uptake of adriamycin by sarcoma transplants in the rat kidney: effects of renal arterial vs systemic constant rate infusion and of combination with ricin.
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.
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
D004317:Doxorubicin; D012276:Ricin