Potentiation of antitumor activity of 1-phthalidyl 5-fluorouracil by acetazolamide.
The effect of acetazolamide (A.A.) on the antineoplastic activity of 1-phthalidyl 5-fluorouracil (PH-FU) against rat and mouse solid tumors was examined. A.A., an inhibitor of liver PH-FU hydrolase, had no antitumor activity but greatly enhanced the activity of PH-FU when coadministered. The potentiation was evaluated in terms of suppression of tumor growth and prolongation of the life-span of tumor-bearing animals. Studies also revealed that A.A. elevated the concentration of PH-FU in tumor tissues, where 5-fluorouracil is slowly liberated from PH-FU. The results are consistent with the hypothesis that A.A. prevents enzymic degradation of PH-FU in the liver and promotes its distribution into target organs.
D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D009368:Neoplasm Transplantation; D051381:Rats; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000378:metabolism
D000970:Antineoplastic Agents; C043972:1-phthalidyl-5-fluorouracil; D000086:Acetazolamide; D005472:Fluorouracil