国产伊曲康唑胶囊剂的生物等效性研究

 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5 minpo200 mg单剂量受试和对照制剂并采集72 h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t_max,c_max,AUC和t_1/2等。按新药审评标准对AUC和c_max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：t_max分别为(4.6±1.3)和(4.1±1.3)h,c_max分别为(319.2±162.2)和(289.0±110.4)ng·mL^-1，t_1/2β分别为(23.8±4.7)和(23.2±4.8)h,AUC_0～∞分别为(5080.5±2451.3)和(4652.1±1610.0) ng·h·mL^-1。两组间各参数均无统计学差异(P＞0.05)。双单侧检验结果分别为t(H)_AUC=2.1598,t(L)_AUC=3.4587,t(H)c_max=3.3420和t(L)c_max=4.5615,t_0.05(16)=1.746;P值均小于0.05。结论国产胶囊剂的相对生物利用度为102.27%；国产伊曲康唑胶囊与斯皮仁诺胶囊为等效制剂。

Study on bioequivalence of domestic itraconazole capsules

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) 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 t_max,c_max,t_1/2 and AUC_0～∞ 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.