盐酸氟桂利嗪胶囊人体生物等效性研究

Bioequivalence of flunarizine hydrochloride capsules

目的:研究2种盐酸氟桂利嗪胶囊的生物等效性。方法:采用两制剂双周期自身对照交叉试验设计,18例健康男性志愿者分别口服单剂量2种盐酸氟桂利嗪胶囊各20 mg(参比制剂和受试制剂),用高效液相色谱(HPLC)紫外检测法测定血浆中氟桂利嗪的浓度,采用DAS1.0程序对药动学参数进行方差分析和双单侧t检验。结果:参比制剂和受试制剂在受试者体内的药动学参数分别为:Cm ax(74.76±16.14)和(70.50±14.96)μg.L-1;Tmax(2.61±0.53)和(2.53±0.36)h;t1/2(6.45±1.13)和(6.48±1.19)h;AUC0-24 h(693.7±170.7)和(686.7±187.4)μg.h.L-1,AUC0-∞分别为(753.4±178.5)和(746.1±189.8)μg.h.L-1,受试制剂对参比制剂的平均相对生物利用度F0-∞为(99.7±16.2)%。AUC0-24 h90%置信区间为0.921-1.049,Cm ax90%置信区间为0.893-1.000,Tm ax经非参数法检验,差异无统计学意义。结论:2种盐酸氟桂利嗪胶囊生物等效。

Objective： To study the pharmacokinetics and hioequivalence of flunarizine hydrochloride capsules. Methods： 18 healthy male volunteers were randomly administered with an oral single crossover dose of test and reference fiunarizine capsules 20 rag. The plasma samples from the volunteers were collected to measure flunarizine concentrations by HPLC-UV. The pharmacokinetic parameters as well as bioequivalence of both flunarizine capsules were analyzed using DAS1.0 program, ANOVA and two-onesided t-test. Results： The main pharmacokinetic parameters of the reference and test flunarizine capsules were as follows ： Cmax （74. 76 ± 16. 14） vs. （70. 50 ± 14. 96）μg· L^ -1, Tmax （2. 61 ± 0. 53 ） vs. （2. 53 ± 0. 36） h, t1/2（6.45 ±1.13）vs. （6.48 ± 1.19）h, AUC0-24h （693.7 ± 170.7）vs. （686.7 ± 187.4）μg·h·L^-1 and AUC0-∞ （753.4 ± 178.5）vs. （746. 1± 189. 8）μg·h·L-1. The relative bioavailability of test capsules was F0-∞（99.7 ± 16.2）%. The 90% confidence interval of AUC0-24h and Cmax was 0.921 - 1.049 and 0.893 - 1. 000, respectively. Conclusion ： The reference and test flunarizine capsules were bioequivalent.