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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 compare the pharmacokinetics and bioavailability of fluconazole in healthy volunteers. Methods: Twenty healthy volunteers were randomized to receive two doses of fluconazole (reference preparation and test preparation) with 150 mg each. The blood concentrations were determined by HPLC. The determination of fluconazole in plasma was carried out by liquid one-liquid extraction (LLE) -HPLC with the linear range of 0.1 ~ 20 mg · L-1 and the lowest detection concentration of 0.10 mg · L-1. The extraction recovery was> 71% (N = 5). The recovery rate was 101.0% ~ 102.5%. The RSD was less than 5.6% and the intraday RSD was no more than 5.0%. Results: The Cmax of the reference preparation and the test preparation were 4.3 ± 1.29gm · L-1 and 4.4 ± 0.82mg · L-1, respectively. The tmax were 0.94 ± 0.7h and 0.89 ± 0.7h respectively, and t1 / 2 was 39.4 ± 8.6h and 39.4 ± 10.9h, indicating that fluconazole capsules have the characteristics of fast absorption and slow elimination after oral administration; AUC0 → t were 152.8 ± 26.6mg · h · L-1 and 155.8 ± 25.3mg · h · L- 1, AUC0 → ∞ were 174.1 ± 34.6 mg · h · L-1 and 177.9 ± 29.1 mg · h · L-1, respectively. There was no significant difference in pharmacokinetic parameters (P> 0.05). From this, the Frel of the test formulation relative to the reference formulation was 104.0% ± 20.0%. Conclusion: The pharmacokinetic parameters of fluconazole in healthy volunteers are similar and bioequivalent.