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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120mg3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tmax,cmax和AUC0～∞。根据被测不同片剂间AUC0～∞之比得出相对生物利用度(F);并将AUC0～∞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tmax分别为(0.6±0.2),(1.1±1.2),(0.5±0.1),(0.5±0.2)h;cmax分别为(108.8±59.5),(56.1±30.7),(73.2±34.9),(94.7±41.1)ng·ml-1;AUC0～∞分别为(175.4±77.9),(135.8±62.4),(154.8±69.5),(1545±51.6)ng·h·ml-1。B,C和D对于A的相对生物利用度分别为83.7%,93.1%,97.6%,90%置信区间结果显示,B,C和DAUC0～∞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。
OBJECTIVE: To evaluate the relative bioavailability and bioequivalence of 4 commercially available nimodipine oral tablets. Methods: Twelve healthy subjects were selected and randomly divided into four groups: oral administration of 120mg of 3 domestic nimodipine tablets (B, C, D) and nimodipine (A) of Bayer Pharmacy in Germany. Plasma concentration was measured by HPLC in our laboratory. Individual bioavailability parameters, tmax, cmax and AUC0 ~ ∞, were obtained according to non-compartmental model analysis of PCNONLIN program. The relative bioavailability (F) was calculated according to the ratio of AUC0 ~ ∞ between different tablets. The logarithm transformation of parameters such as AUC0 ~ ∞ was performed. Based on the analysis of variance, double unilateral test was used to evaluate the bioequivalence . Results: The tmax of A, B, C and D were (0.6 ± 0.2), (1.1 ± 1.2), (0.5 ± 0.1) and (0.5 ± 0.2) h respectively; the cmax were (108.8 ± 59.5) and 30.7, 73.2 ± 34.9 and 94.7 ± 41.1 ng · ml-1, respectively. The AUC0 ~ ∞ were (175.4 ± 77.9), (135.8 ± 62.4), (154.8 ± 69.5) and (1545 ± 51.6) ng · h · ml-1. The relative bioavailability of B, C and D to A were 83.7%, 93.1% and 97.6% respectively. The 90% confidence interval showed that the average values of B, C and DAUC0 ~ ∞ were 66.7% ~ 88.8% of A, 77.2% % ~ 102.7% and 80.5% ~ 107.1%, D and A have bioequivalence.