The pharmacokinetics of doxifluridine and 5-fluorouracil after single intravenous infusions of doxifluridine to patients with colorectal cancer.
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.
Schaaf
L J
LJ
Department of Pharmacy, University of Otago Medical School, Dunedin, New Zealand.
Dobbs
B R
BR
Edwards
I R
IR
Perrier
D G
DG
D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged
D005467:Floxuridine; D005472:Fluorouracil; C025034:doxifluridine