国产伊曲康唑胶囊剂的生物等效性研究

Study on bioequivalence of domestic itraconazole capsules

目的 以进口伊曲康唑胶囊 (商品名斯皮仁诺胶囊 )为对照品对国产伊曲康唑胶囊剂进行生物等效性评价。方法 18名健康成年男性受试者采用随机交叉分组自身对照试验设计 ,分别于标准早餐后 5minpo 2 0 0mg单剂量受试和对照制剂并采集 72h内动态血标本 ;用改进的HPLC测定血清中药物浓度并计算相关参数tmax,cmax,AUC和t1/ 2 等。按新药审评标准对AUC和cmax进行双单侧t检验以判定两制剂是否生物等效。结果 测试品和对照品生物利用度参数 :tmax分别为 (4 .6± 1.3)和 (4 .1± 1.3)h ,cmax分别为 (319.2± 16 2 .2 )和 (2 89.0± 110 .4)ng·mL-1,t1/ 2 β分别为 (2 3.8± 4.7)和 (2 3 .2± 4.8)h ,AUC0～∞ 分别为(5 0 80 .5± 2 45 1.3)和 (4 6 5 2 .1± 16 10 .0 )ng·h·mL-1。两组间各参数均无统计学差异 (P >0 .0 5 )。双单侧检验结果分别为t(H) AUC=2 .15 98,t(L) AUC=3.45 87,t(H) cmax=3 .342 0和t(L) cmax=4.5 6 15 ,t0 .0 5( 16) =1.746 ;P值均小于 0 .0 5。结论 国产胶囊剂的相对生物利用度为 10 2 .2 7% ;

OBJECTIVE: To study the bioequivalence of itraconazole (ITZ) capsule in healthy volunteers. METHODS: A rapid and sensitive RP-HPLC assay was modified for the determination of the drug levels in serum. In a randomized two-way crossover design, 200 mg single dose po domestic (A) and imported (B, sporanox [registered trademark] ) ITZ capsules, respectively, were given to 18 male healthy volunteers. The parameters were estimated by the non-compartment model with a statistic analysis of ANOVA and two one-sided t test. RESULTS: The tmax, cmax, t1/2 and AUC0 [similar to] infinity of A and B were (4.6 ± 1.3) and (4.1 ± 1.3) h, (319.2 ± 162.2) and (289.0 ± 110.4) ng·mL-1, (23.8 ± 4.7) and (23.2 ± 4.8) h, (5080.5 ± 2451.3) and (4652.1 ± 1610.0) ng·h·mL-1, respectively. The mean relative bioavailability of product A vs. reference B was 102.27%. There was no significant difference between the two products. CONCLUSION: The results suggested that these two products were bioequivalent.