Absorption of 5′-Deoxy-5-fluorouridine from Colon

Abstract

Rectally administered 5′-deoxy-5-fluorouridine (dFUR) is active against transplanted dimethylhydrazine-induced colon tumor in rats. This study investigated the disposition of dFUR in normal non-tumor-bearing rats after rectal administration (350 or 700 mg/kg). An intravenous (iv) bolus injection of [5′-³H]dFUR (28.2 µCi, 0.43 µg) was given 5 min after the rectal dose (700 mg/kg) to determine the dFUR clearance (CL). Blood and fecal samples were analyzed by high-pressure liquid chromatography and liquid scintillation. After the iv tracer dose, the CL was 19 ml/min/kg and the terminal half-life was 50 min. After a 700-mg/kg rectal dose, the terminal half-life was 430 min, the bioavailability was 30%, and the fraction of the dose recovered in 24-hr feces was 34%. After a 350-mg/kg dose, absorption was apparently not completed at 12 hr, as indicated by a lack of decline in blood concentration. The bioavailability of the 350-mg/kg dose exceeded 16%. The absorption of dFUR (700 mg/kg) from the colon was analyzed by the Loo–Riegelman method; the absorption half-life was 550 min. The terminal half-life after the rectal dose was much slower than that after the iv tracer dose but similar to the absorption half-life. These data indicate that dFUR was absorbed from the colon, that the absorption process was the rate-limiting step of its disposition after rectal administration, and that the slow absorption gave a sustained drug concentration in blood.