Pharmacokinetic studies of 5-fluorouracil after oral and intravenous administration in man

The pharmacokinetic conditions for oral administration of 5-fluorouracil (5-FU) were investigated in 16 patients with malignant liver tumours. The concentration of 5-FU in portal and systemic blood was determined by a microbiologic method every 10 min. during 2 hours after oral or intravenous administration of a standard dose of 250 mg 5-FU ( approximately 4 mg/kg b. wt.) or 15 mg 5-FU/kg b. wt. The drug was rapidly absorbed after oral administration with peak values within 10-30 min. 25% of the lower and 40% of the higher oral dose reached the systemic circulation. The reduction of systemic bio-availability was partly accomplished by a loss in the gastrointestinal tract and partly by extraction by the liver. The hepatic extraction ratio was calculated to 0.56 and 0.26 after the lower and the higher dose respectively indicating a saturable process. The availability of 5-FU was significantly higher in portal blood than in systemic blood after oral administration. The opposite conditions were found after intravenous administration. Thus, oral administration of 5-FU to patients with malignant liver tumours seems rational.