Prolonged treatment schedules with intraperitoneal 5-fluorouracil diminish the local-regional nature of drug distribution.

The levels of 5-fluorouracil (5-FU) in plasma and peritoneal fluid were determined after the bolus administration of drug in 2 L of dialysis fluid through a Tenckhoff catheter into the peritoneal cavity of colon cancer patients. An increasing dose of intraperitoneal (i.p.) 5-FU resulted in an increased level of 5-FU in the blood. In 18 treatment cycles studied in four patients, the clearance of 5-FU from peritoneal fluid and the level of drug in the plasma were increased by day 5 of i.p. treatment. In one of these patients, the peritoneal clearance of 5-FU did not further increase between days 8 and 12. If ascites fluid was not removed prior to subsequent 5-FU administration, drug absorption from the peritoneal cavity was markedly decreased. These studies show that a dose of 5-FU given within a body compartment may profoundly affect the pharmacokinetics of subsequent doses of the same chemotherapy.