Pharmacokinetics of 5-fluorouracil infusions in the rat: comparison with man and other species.

Abstract:

: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.

authors

Collins JM

doi

10.1007/BF00434346

subject

Has Abstract

pub_date

1985-01-01 00:00:00

pages

108-11

issue

2

eissn

0344-5704

issn

1432-0843

journal_volume

14

pub_type

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