Pharmacokinetics of four 5-FU preparations administered rectally to rats and rabbits

AIM: To compare the pharmacokinetic characteristics of four preparations of fluorouracil (5-FU) administered rectally using a rat model. METHODS: Concentrations of 5-FU were measured in plasma, the rectal wall and mesentery lymph tissues of rats and rabbits by high performance liquid chromatography. Differences between the main pharmacokinetic parameters were compared by statistical analysis. RESULTS: The 5-FU concentrations in the rectal wall and mesenteric lymph tissues were significantly higher than the concentration in blood following rectal administration for all four of the preparations (P < 0.01). The drug level in the rectal wall was higher in the animals received delivery of an emulsion, compared to those who received delivery as a suppository (P < 0.05). Moreover, the animals who received a lipophil-based suppository had lower plasma level of drug than those who received a hydrophil-based suppository, and the animals who received the simple (o/w) emulsion had lower plasma level than those who received the complex (w/o/w) emulsion. The differences found in the rat model were confirmed in rabbits (P < 0.01). CONCLUSION: The lipophil-based suppository and the simple emulsion of 5-FU might be more suitable for rectal administration for treatment of rectal cancers.