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.
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Schaaf, L.J., Dobbs, B.R., Edwards, I.R. et al. The pharmacokinetics of doxifluridine and 5-fluorouracil after single intravenous infusions of doxifluridine to patients with colorectal cancer. Eur J Clin Pharmacol 34, 439–443 (1988). https://doi.org/10.1007/BF01046699
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DOI: https://doi.org/10.1007/BF01046699