5-氟尿嘧啶结肠定位壳聚糖微球在大鼠体内的药物动力学及生物利用度考察

目的对结肠定位壳聚糖微球的体内药物动力学及生物利用度进行考察,为壳聚糖微球在结肠肿瘤治疗领域的应用提供理论依据。方法用HPLC法测定大鼠口服5-氟尿嘧啶壳聚糖微球(受试制剂)和5-氟尿嘧啶溶液(参比制剂)后不同时间点血浆中5-氟尿嘧啶的质量浓度,计算药物动力学参数和相对生物利用度。结果微球和溶液的ρmax分别为(30.16±2.870)mg.L-1和(13.23±2.817)mg.L-1,tmax分别为(8.333±1.505)h和(1.042±0.400)h,相对生物利用度为215.42%。结论5-氟尿嘧啶壳聚糖微球与溶液剂相比,具有一定的结肠定位性和缓释性,且相对生物利用度高。

Pharmacokinetics-and-bioavailability of colon-specific fluorouracil-loaded chitosan microspheres in mice

Abstract: Objective To study the pharmacokinetics and relative bioavailability of fluorouracil-loaded chitosan microspheres in mice and provide the evidences in the colon-specific fields. Methods The plasma levels of fluorouracil at different time points were determined by HPLC after oral administration of a single dose of the self-made microspheres (test formulation) and solution (reference formulation) to mice.The pharmacokinetics and relative bioavailability were analyzed. Results The ρmax values of solution and microspheres were （30.16±2.870）mg·L-1 and （13.23±2.817）mg·L-1. The tmax values were（1.042±0.400）h and （8.333±1.505）h, the relative bioavailability was 215.42%. Conclusion Compared with solution, the self-made microspheres are proved to be colon-specific with sustained release property.