Journal article
Pharmacokinetic studies of 5-fluorouracil and 5'-deoxy-5-fluorouridine in rats
The Journal of pharmacology and experimental therapeutics, Vol.227(1), pp.174-180
1983
DOI: 10.1016/S0022-3565(25)21961-9
PMID: 6225866
Abstract
The pharmacokinetics of 5-fluorouracil (FU) and its metabolic prodrug, 5'-deoxy-5-fluorouridine (dFUR), were investigated in 5- to 9-month-old rats without tumors. Intravenous bolus injections and infusions of FU (25-35 mg X kg-1) and dFUR (500-750 mg X kg-1) had activity against transplanted colon tumors in 2- to 4-month-old rats. Blood and plasma concentrations of FU and dFUR were analyzed by high-pressure liquid chromatography using 5-bromouracil as the internal standard. Free fractions of these drugs in plasma were indistinguishable from unity, indicating little or no protein binding. The area under the blood concentration-time profiles and the steady-state concentrations of unchanged dFUR were 40- to 100-fold higher than those of unchanged FU. The respective blood clearances of FU and dFUR were 44 and 18 ml X kg-1 X min-1 after i.v. bolus injections, which were significantly lower than the 108 and 26 ml X kg-1 X min-1 after infusion. FU clearance decreased when its infusion rate was increased from 25 to 50 mg X kg-1 X day-1. Renal clearances of both drugs remained the same after either route of administration. These data suggest that both drugs were eliminated by nonlinear kinetics and that their metabolism was saturated at a more rapid administration rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Details
- Title: Subtitle
- Pharmacokinetic studies of 5-fluorouracil and 5'-deoxy-5-fluorouridine in rats
- Creators
- J. Lai-Sim Au - The Ohio State UniversityJudy S Walker - The Ohio State UniversityYoucef Rustum - The Ohio State University
- Resource Type
- Journal article
- Publication Details
- The Journal of pharmacology and experimental therapeutics, Vol.227(1), pp.174-180
- Publisher
- American Society for Pharmacology and Experimental Therapeutics
- DOI
- 10.1016/S0022-3565(25)21961-9
- PMID
- 6225866
- ISSN
- 0022-3565
- eISSN
- 1521-0103
- Language
- English
- Date published
- 1983
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359684502771
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