Study On Tissue Distribution And Targeting Evaluation Of A Novel Proliposomal Preparation Of Tegafur

Objective: In order to improve the physical stability of liposome dispersions, a novel proliposomal preparation containing tegafur was developed by using a simple technology, thus providing an effective way for commercialization of this new formulation. The aim of the study was to evaluate tissue distribution of this preparation in Wistar rats in comparison to that of tegafur tablet, and demonstrate its tissue targetability by the use of some pharmacokinetic parameters to assessing tissue targeting. Methods: Concentrations of tegafur in tissues or plasma were measured by high performance liquid chromatography and external standardization method was applied following oral administration of proliposomal preparation of tegafur(PL-FT207) or tegafur tablet(T-FT207) to rats. The HPLC system consisted of Kromasil ODS-lcolumn ( Φ4.6× 250mm,5μm) and UV detector operated at 270nm. The mobile phase was methanol-water (24:76),the flow-rate was 1.0ml/min,the column temperature was 25.0℃,and the injection volume was 5μ1. The data were processed with 3p87 programs; the pharmacokinetic parameters were obtained and analyzed in order to evaluate tissue targeting. Results: The area under the concentration-time curve(AUC) was significantly increased in plasma, liver, kidney, colon and lung(p<0.01) of PL-FT207 group in contrast to that of T-FT207 group, the relative tissue efficiencies of these tissues were 1.34-1.66, while the AUC in brain and heart of PL-FT207 had no significant difference compared with that of T-FT207(p>0.5), and the relative tissue efficiencies was about l,but themaximum drug concentrations of these two tissues were significantly declined (p<0.005) ,and the MRT of PL-FT207 group were significantly prolonged in most tissues except colon compared to that of T-FT207(p<0.002). Conclusion: The novel proliposomal preparation of tegafur is able to increase drug distribution in kidney, liver, colon and lung, and decrease the maximum drug concentration in brain and heart. These effects may contribute to the reduced toxicity of tegafur in CNS and heart, thus providing scientifical basis for further studies on this formulation.