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

Eight patients with malignancies confined to the peritoneal space part icipated in this study. Five hundred milligrams 5-fluorouracil or 10 m g mitomycin C was diluted in 1 L saline. The mixed solution was inject ed intraperitoneally through the semi-permanent peritoneal catheter. B lood and peritoneal fluid were collected after injection. 5-Fluorourac il concentrations in the peritoneal fluid were 1000 times those in ser um, while mitomycin C concentrations were 100 times those in serum. Ar eas under the concentration vs time curve (AUC) were calculated by the trapezoidal method with extrapolation to infinity. The ratio of perit oneal fluid AUC to serum AUC was about 1400 for 5-fluorouracil and 80 for mitomycin C. Patterns for the absorption and elimination from syst emic circulation were similar for both compounds. Drug concentrations in the peritoneal fluid and serum were analysed according to the compa rtment 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 appar ent volume of distribution (Vd(s)/F) and clearance in the peritoneal c avity (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)).