RESUMO
OBJECTIVE: To study the distribution of 5-FU in rat plasma and liver tissue following systemic or local 5-FU infusion. METHODS: 5-FU was administered at the dose of 20 mg/kg systemically via bolus injection through the jugular vein or locally via infusion through the hepatic artery and portal vein of the rats. High-performance liquid chromatography was used to measure 5-FU concentration in the plasma and liver tissue, and the pharmacokinetic parameters, penetration rate and therapeutic dominance of 5-FU were calculated. RESULTS: Systemic administration of 5-FU resulted in the peak 5-FU concentration (Cmax) and area under curve (AUC) in the liver tissue of 13.79-/+4.56 microg/g and 342.20-/+108.20 microg.min(-1).g(-1)g-1, with the plasma Cmax and AUC of 36.85-/+5.96 microg/g and 842.00-/+158.00 microg.min(-1).ml(-1), respectively. Local 5-FU administration through the hepatic artery resulted in Cmax and AUC in the liver tissue of 29.58-/+4.30 microg/g and 794.60-/+115.40 microg.min(-1).g(-1) and Cmax and AUC in the plasma of 24.39-/+4.63 microg/g and 639.70-/+133.80 microg.min(-1).ml(-1), respectively. After administration through the portal vein, the Cmax and AUC of 5-FU was 28.21-/+4.46 microg/g and 733.60-/+180.3 microg.min(-1).g(-1) in the liver tissue, and 21.02-/+4.06 microg/ml and 529.80-/+111.50 microg.min(-1).ml(-1) in the plasma, respectively. CONCLUSION: Compared with systemic venous bolus injection, administration through the hepatic artery and portal vein can significantly increase 5-FU concentration in the liver, and decrease its concentration in the peripheral blood.
