Pharmacokinetics of 5-fluorouracil infusions in the rat: comparison with man and other species.
Saturable elimination of 5-FU is exhibited in rats during constant infusions. Over the range of 3-480 mg/m2/h, total-body clearance of 5-FU decreases from 600 ml/min/m2 to less than 90 ml/min/m2. Previously published values for catabolism of 5-FU by rat hepatocytes can be used to simulate the plasma concentrations of 5-FU that were measured over this range of infusions. The qualitative pattern of nonlinear pharmacokinetics for 5-FU is similar in rats, dogs, monkeys, and humans. However, there are major quantitative differences in total-body clearance values, expressed in terms of surface area (ml/min/m2) or as a fraction of cardiac output. Rat and monkey have substantially lower 5-FU clearance values than dog and man. Although 5-FU clearance values were similar in dogs and humans, total body clearance values for thymidine are 18-fold higher in humans than in dogs. The selection of an appropriate animal model to pursue the clinical observations of high total body clearance of pyrimidines remains uncertain.
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D005260:Female; D005472:Fluorouracil / Q000097:blood*; D000882:Haplorhini; D006801:Humans; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains
D005472:Fluorouracil