Tumor uptake of vincristine during close arterial vs systemic constant-rate infusion: experiments on sarcoma transplants in the rat kidney.
The uptake of vincristine (VCR) by normal tissues and by sarcomas transplanted to both kidneys in rats was studied at 10 min after constant rate infusion of 1 mg/kg body wt into one renal artery for 3, 10 and 30 min. Since the selectively infused kidney extracted only 2.5% of the total dose at the first renal passage, the present model provides a direct comparison between systemic and selective i.a. infusion of VCR in each animal. Tumor VCR uptake was 2.8 times higher and the corresponding blood VCR concentration time product about 4 times higher on the selectively infused side than on the contralateral side. Reduction of renal blood flow by clamping the selectively infused renal artery raised the local VCR blood concentration by another 10 times during 10 min infusion and further doubled the tumor uptake of VCR. Thus a 5-6 times higher VCR concentration in the tumor was achieved as compared to that obtainable by systemic administration of the same total dose. The results are compatible with a saturable mechanism of VCR uptake by renal tissue and tumors.
D000818:Animals; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism*; D008297:Male; D009368:Neoplasm Transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D012077:Renal Artery; D012513:Sarcoma, Experimental / Q000378:metabolism*; D013997:Time Factors; D014750:Vincristine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*
D014750:Vincristine