ISSN:
1432-1041
Keywords:
doxifluridine
;
colorectal carcinoma
;
5′-deoxy-5-fluorouridine
;
5-fluorouracil
;
pharmacokinetics
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Summary The disposition kinetics of a new 5-fluorouracil prodrug, 5′-deoxy-5-fluorouridine (5′dFUR, doxifluridine), were investigated in six patients with colorectal carcinoma. Each patient randomly received two single intravenous doses of 5′dFUR (2 and 4 g · m−2) on separate days. Plasma concentrations of 5′dFUR fell rapidly with terminal half-lives ranging from 16.1 to 27.7 min. A disproportionate increase in the area under the curve with increasing dose was seen in most patients. Doubling the dose resulted in a 40% decrease in nonrenal clearance (0.60 to 0.37 l · min−1) but no apparent change in renal clearance (0.32 to 0.29 l · min−1) or steady-state apparent volume of distribution (19.8 to 20.4 l). The mechanism for dose-dependence of 5′dFUR appears to be primarily due to nonlinear elimination associated with nonrenal processes rather than nonlinear plasma protein or tissue binding.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01046699
