4种市售尼莫地平口服片剂的相对生物利用度及生物等效性评价

 目的：评价4种市售尼莫地平口服片剂的相对生物利用度和生物等效性。方法：选择12名健康受试者，采用随机交叉四组试验，分别口服120mg 3种国产尼莫地平片(B，C，D)与德国拜尔药厂的尼莫通片(A)。血药浓度由本实验室改进的高效液相色谱法测得，按照PCNONLIN程序非房室模型型分析法获得个体生物利用度参数t_max，c_max和AUC_o～∞。根据被测不同片剂间AUC_o～∞之比得出相对生物利用度(F)；并将AUC_o～∞等参数对数转换，在方差分析基础上再行双单侧检验进行生物等效性评价。结果：A，B，C和D的t_max。分别为(0.610.2)，(1.1士1.2)，(0.5土0.1)，(0.5士0.2)h；c_max分别为(108.8士59.5)，(56.1士30.7)，(73.2士34.9)，(94.7士41.1)ng·ml^-1；AUC_o～∞分别为(175.4士77.9)，(135.8士62.4)，(154.8士69.5)，(154.5士51.6)ng·h·ml^-1B，C和D时于A的相时生物利用度分别为83.7%，93.1%，97.6%，90%置信区间结果显示，B，C和D AUCo平均值分别为A的66.7%～88.8%，77.2%～102.7%和80.5%～107.1%，D与A具有生物等效性。

Study of the bioequivalence of four formulations of nimodipine in healthy volunteers

OBJECTIVE: The objective was to compare the bioavailability and bioequivalence of four generic marketing formulations. METHODS: The study design was a single-dose, randomized fou-way crossover with a 1-week washout period between each phase of the experiment dosing. Plasma concentration-time profiles were determined and the bioavailabilities of different formulations of nimodipine tablets (A,B, C and D )following oral administration of a 120mg nimodipine single dose were compared. RESULTS:The t_maxof the tablet A, B, C and D was (0.6 ± 0.2) , (1.1 ± 1.2), (0.5 ± 0.1) and (0.5 ± 0.2) h, respectively; the c_maxwas (108.8 ± 59.5), (56.1 ± 30.7), (73.2±34.9) and (94.7 ± 41.1) ng·ml^-1, respectively; and the AUC was (175.4 ± 77.9) , (135.8 ±62.4 ), (154.8 ± 69.5) and (154.5 ± 51.6)ng·h·ml_max, respectively. The relative bioavailabilities of tablet B, C and D compared with tablet A were 83.7%, 93.1% and 97.6%, respectively. The 90% confidence interval for the AUC shown for tablet B and C were 66.7～88.8% and 77.2～102.7%, respectively, less than 80% compared to the reference at the low-range estimate; tablet D was 80.5～107.1%, greater than 80% compared to the reference at the low-range estimate. CONCLUSION: The 90% confidence interval with respect to AUCwas between 80% and 125%, the formulation B and C were not considered bioequivalent, formulation D was considerded bioequivalent，compared with formulation A.