氟康唑胶囊在健康人体的药代动力学及生物等效性

Pharmacokinetics and bioequivalence of fluconazole capsules in healthy volunteers

目的建立人血浆氟康唑(抗真菌药)HPLC测定法,比较氟康唑2种制剂在健康志愿者体内的药代动力学和相对生物利用度。方法用随机开放交叉试验设计,20名健康志愿者分别单剂量口服试验和参比制剂氟康唑胶囊300mg,用高效液相色谱法法测定血药浓度,计算2制剂的药代动力学参数,并进行生物等效性评价。结果试验和参比制剂氟康唑胶囊的主要药代动力学参数t1/2分别为(31.20±3.98),(31.51±3.26)h;tmax分别为(2.83±0.37),(2.65±0.24)h;Cmax分别为(6.20±1.08),(6.11±1.01)μg·mL-1;AUC0-96分别为(208.42±21.77),(200.27±18.27)μg·h·mL-1;AUC0-∞分别为(234.00±24.56),(227.14±20.91)μg·h·mL-1。各药代动力学参数无显著性差异(P>0.05)。试验制剂氟康唑胶囊相对生物利用度F为(104.3±8.5)%。结论2制剂具有生物等效性。

Objective To establish an HPLC method for studying pharmacokinetics and relative bioavailability of fluconazole in healthy volunteers. Methods A single dose 300 mg of reference and test fluconazole capsules was given to 20 healthy volunteers in a randomized 2 -way cross - over study. The plasma fluconazole concentrations were determined by HPLC. The pharmacokinetics as well as relative bioavailability were measured. Results The pharmacokinetic parameters of flueonazole test and reference were as follows： t1/2 were （31.20 ± 3.98） h and （31.51 ± 3.26） h, tmax were （2.83 ± 0.37 ） h and （2.65 ± 0.24） h, Cmax were （6.20±1.08） μg·mL^-1 and （6.11 ±1.01）μg·mL^-1, AUC0-96 were （208.42 ±21.77） μg·h·mL^-1 and （200.27 ± 18.27） μg·h·mL^-1, AUC0-∞ were （234.00 ±24.56） μg·h·mL^-1and （227.14 ±20.91 ） μg·h·mL^-1, and there were no siginificant differences between the two formulations （ P 〉 0.05 ）. The relative bioavailability of the tested fluconazole was （ 104.3 ± 8.5 ） %. Conclusion The reference and test fluconazole capsules are bioequivalent.