国产甲泼尼龙片剂的生物等效性研究

Study on bioequivalence of domestic methylprednisolone tablets

目的 用进口片剂 (A)为对照品 ,评价国产片剂 (B)的相对生物利用度和生物等效性。方法 采用随机交叉分组试验设计 ,18名健康成年男性受试者分别以 15 0mL牛奶空腹送服单剂量 40mg测试品和对照品 ,按设计采集 14h内动态血标本 ;用一改进的HPLC测定血浆药物浓度 ,以非房室模型计算AUC和t1/2 ,tmax和cmax为实测值。按新药审评标准对AUC和cmax进行方差分析和双单侧t检验 ,以判定两制剂是否生物等效。结果 对照品和测试品的tmax分别为 ( 2 .1± 0 .5 )h和 ( 1.9± 0 .5 )h ,cmax分别为 ( 5 72 .6± 12 1.7)ng·mL-1和 ( 5 97.6± 119.8)ng·mL-1,AUC0 -∞ 分别为 ( 2 5 71.2± 6 47.4)h·ng·mL-1和 ( 2 5 2 8.4± 5 5 8.8)h·ng·mL-1,t1/2 分别为 ( 2 .3± 0 .4)h和 ( 2 .2± 0 .4)h ;片剂B相对A的平均生物利用度为 99.6 2 %。结论 统计分析显示 。

OBJECTIVE: To study the bioequivalence of methylprednisolone (MP) tablets in healthy volunteers. METHOD: A rapid and sensitive RP-HPLC assay was modified for the determination of the drug levels in plasma. In a randomized two-way crossover design, 40 mg single dose po domestic (B) and imported (A, Medrol™) MP tablets, respectively, were given to 18 male healthy volunteers. The parameters were estimated by non-compartment model with a statistic analysis of ANOVA and two one-side t-test. RESULTS: The tmax, cmax, t1/2 and AUC0-∞ of tablet-B and-A were (1.9 ± 0.5) h and (2.1 ± 0.5) h, (597.6 ± 119.8) ng&middotmL-1 and (572.6 ± 121.7) ng&middotmL-1, (2.2 ± 0.4) h and (2.3 ± 0.4) h, (2528.4 ± 558.8) h&middotng&middotmL-1 and (2571.2 ± 647.4) h&middotng&middotmL-1, respectively. The mean relative bioavailability of the tablet-B vs A was 99.62%. There was no significant difference between the two products. CONCLUSION: The results suggested that these two products were bioequivalent.