非诺贝特-羟丙基-β-环糊精包合物在大鼠体内的药动学及生物利用度研究

Pharmacokinectics and relative bioavailability of fenofibratehydroxypropyl-β-cyclodextrin complex in rats

目的 研究非诺贝特（FNB）-羟丙基-β-环糊精（HP-β-CD）包合物在大鼠体内的药动学及生物利用度。方法 大鼠分别灌胃给予FNB原药及其HP-β-CD包合物,采用HPLC法测定给药后不同时间的血药浓度,并采用3P97药动学程序计算药动学参数。结果 FNB及其HP-β-CD包合物在大鼠体内的药动学过程符合开放一室房室模型。主要药动学参数tmax分别为（6.67±3.50）h和（3.17±2.62）h,Cmax分别为（6.31±3.04）μg.mL^-1和（39.82±16.25）μg.mL^-1,AUC0～t分别为（81.36±51.00）μg.h.mL^-1和（462.74±196.68）μg.h.mL^-1,AUC0～∞分别为（90.34±51.72）μg.h.mL^-1和（483.90±260.92）μg.h.mL^-1,2组间差异有显著统计学意义（P〈0.01）;FNB包合物的相对原药生物利用度为535.6%。结论 FNB与HP-β-CD形成包合物后,其在大鼠体内的吸收速度明显加快,生物利用度显著提高。

Objective To study the pharmacokinetics and relative bioavailability of FNB-HP-β-CD complex in rats. Methods FNB and its HP-β-CD complex were administered orally to 2 groups of rats. The plasma fenofibric acid concentrations at different time intervals following the administration was determined by HPLC. The pharmacokinetic parameters were estimated by 3P97 pharmacokinetic program. Results The in vivo pharmacokinetic process in rats for FNB and its HP-β-CD complex followed the one-compartment open model. The main pharmacokinetic parameters were as follows： tmax were （6.67±3.50） h and （3.17±2.62） h, Cmax were （6.31 ±3.04） μg · mL^- 1 and （39.82± 16.25） μg · mL^- 1, AUC0-twere （81.36±51.00） μg ·h· mL^- 1 and （462.74±196.68） μg ·h· mL^- 1, AUC0-∞ were （90.34±51.72） μg ·h· mL^- 1 and （483.90±260.92）μg ·h· mL^- 1. There was significant difference in the pharmacokinetic param- eters such as tmax, Cmax and AUC0-∞ between FNB and its HP-β--CD complex groups （P 〈 0.01）. The relative bioavail- ability of the FNB- HP-β-CD complex was 535.6%. Conclusion The absorption rate, especially the plasma drug peak concentration and bioavailability of the drug in rats are significantly increased when FNB is included with HP-β-CD.