PHARMACOKINETIC CHARACTERISTICS OF 5-FLUOROURACIL AND MITOMYCIN-C IN INTRAPERITONEAL CHEMOTHERAPY

Eight patients with malignancies confined to the peritoneal space participated in this study. Five hundred milligrams 5-fluorouracil or 10 mg mitomycin C was diluted in 1 L saline. The mixed solution was injected intraperitoneally through the semi-permanent peritoneal catheter. Blood and peritoneal fluid were collected after injection. 5-Fluorouracil concentrations in the peritoneal fluid were 1000 times those in serum, while mitomycin C concentrations were 100 times those in serum. Areas under the concentration vs time curve (AUC) were calculated by the trapezoidal method with extrapolation to infinity. The ratio of peritoneal fluid AUC to serum AUC was about 1400 for 5-fluorouracil and 80 for mitomycin C. Patterns for the absorption and elimination from systemic circulation were similar for both compounds. Drug concentrations in the peritoneal fluid and serum were analysed according to the compartment model. The half-life in the peritoneal fluid (t1/2(p)) and the rate constant from the peritoneal fluid to the systemic circulation (k(a)) were nearly equal for both 5-fluorouracil and mitomycin C (t1/2(p) 1.0 h for 5-fluorouracil and 1.3 h for mitomycin C; k(a) 0.71 h(-1) for 5-fluorouracil and 0.68 h(-1) for mitomycin C), although the apparent volume of distribution (Vd(s)/F) and clearance in the peritoneal cavity (CL(p)) for mitomycin C (78 L m(-2) and 1.8 L h(-1) m(-2)) were about twice the values for 5-fluorouracil (149 L m(-2) and 0.8 L h(-1) m(-2)).