THE PHYSIOLOGIC DISPOSITION OF 5-FLUOROURACIL AND 5-FLUORO-2'-DEOXYURIDINE IN MAN.

Abstract

The plasma concentration and the urinary excretion of 5‐fluorouracil (FU) and 5‐fluoro‐2′deoxyuridine (FUdR), administered to patients with cancer, were determined by microbiologic assay; following regional administration, both local and systemic concentrations were measured. Rapid intravenous injections of usual clinical doses resulted in relatively high initial plasma concentrations (100 to 750 mμM per milliliter) which fell below a detectable level by 3½ hours in all patients. Generally, less than one fifth of the dose was excreted in the urine and almost all of this occurred in the first hour. The renal clearance of both drugs exceeded the glomerular filtration rate, and the clearance of FUdR was greater than FU. Gastrointestinal absorption of FU was unpredictable; FUdR was very poorly absorbed. Both drugs were degraded more completely when given by continuous infUSion, as indicated by reduced urinary excretion. After intravenous injection, the drug concentration in the cerebrospinal fluid and in neoplastic effusions was only one‐fiftieth or less that of the plasma concentration. After direct injection into neoplastic effusions, the concentration in the fluid was over 100 times that reached in the effusion after intravenous injection of the same dose. Long‐term infusion of low doses of FU into small arteries resulted in 100 or more times greater local than systemic plasma concentrations, while regional perfusion of FUdR resulted (briefly) in up to 1,000 or more times the concentration in the perfusion circuit compared to the general circulation.