氟康唑胶囊的人体药代动力学及其生物利用度比较

The Pharmacokinetics and Relative Bioavailability of Fluconazole in Healthy Volunteers

目的:比较氟康唑两种制剂在健康志愿者体内的药代动力学和生物利用度。方法:20例健康志愿者随机交叉口服氟康唑两种制剂（参比制剂与受试制剂）,各150mg,采用HPLC法测定血中药物浓度。血浆中氟康唑的测定采用液一液提取（LLE）-HPLC法,方法的线性范围为0.1～20mg·L-1,最低检测浓度约为 0.10mg·L-1,提取回收率>71％（n=5）,方法回收率为101.0～102.5％,样品日内RSD≤5.6％,日间RSD为≤5.0％。结果:参比制剂与受试制剂的Cmax分别为4.3±1.29gm·L-1及4.4±0.82mg·L-1,tmax分别为0.94±0.7h及0.89±0.7h,t1/2分别为39.4±8.6h及39.4±10.9h,表明氟康唑胶囊口服后具有吸收快和消除慢的特点;AUC0→t分别为152.8±26.6mg·h·L-1及155.8±25.3mg·h·L-1;AUC0→∞分别为174.1±34.6mg·h·L-1及177.9±29.1mg·h·L-1,各药代动力学参数无显著性差异（P>0.05）。由此算得受试制剂相对于参比制剂的Frel为104.0％±20.0％。结论:氟康唑两种制剂在健康志愿者体内的药代动力学参数相似,具有生物等效性。

OBJECTIVE: To study the pharmacokinetics and relative bioavailability of fluconazole capsules in healthy volunteers. METHOD: Fluconazole in plasma was determined by LLE- HPLC. A linear range was from 0.1-20mg·L-1.Within-day andbetween-day precisions were less than 5.6 %(n=5) and 5.0%(n=5), respectively. The extraction recoveries were more than 71.5 %(n=5) and the method recoveries were 101. 0-102.5% %. Twenty volunteers were enrolled in a randomized crossover study with a single oral dose of 150mg of tested and refered fluconazole. RESULTS: The results showed that the one-compartment open model is used to describe the time course of plasma concentration of fluconazole in twenty volunteers following oral administration of single dose of fluconazole.The pharmacokinetics parameters of the tested and refered fluconazole such as Cmax、tmax、t1/2、AUC0→t and AUC0→∞ were 4.3+1.29mg·L-1and4.4±0.82mg·L-1, 0.94±0.7h and 0.89±0.7h,39.4±8.6hand39.4±10.9h, 152.8±26.6mg·h·L-1 and 155.8±25.3mg·h·L-1,174.1±34.6mg·h·L-1 and 177.9±29.1mg·h·L-1, respectively, and there were no significant differences between the two formulations. (P>0.05). CONCLUSION: The tested and refered fluconazole were of bioequivalence, and the bioavailability of the tested fluconazole was 104.0%±20.0% .