Differential toxicity and pharmacokinetics of sodium and Tris salts of 5-fluorouracil in the rat.
1. Rats injected intraperitoneally (i.p.) with the Tris salt of 5-fluorouracil (1.44 mmol/kg) showed severe toxic symptoms and a 15% mortality. No mortality and no obvious toxicity, apart from intestinal toxicity, resulted after injection of the sodium salt at equimolar dosage. 2. The plasma pharmacokinetics of the two salts of 5-fluorouracil (1.44 mmol/kg) were different after i.p. injection: higher plasma levels were achieved and were sustained for longer after the Tris salt than after the sodium salt. 3. No differences in plasma pharmacokinetics were observed after intra-arterial (i.a.) injection of the two salts of 5-fluorouracil (6.576 mmol/kg). 4. Thus there are fundamental (and potentially important) differences between the biological properties of the sodium and Tris salts of 5-fluorouracil. These cannot be explained at present.
D000818:Animals; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity*; D007700:Kinetics; D008297:Male; D051381:Rats
C031194:5-fluorouracil tromethamine; D005472:Fluorouracil