【摘要】 以进口 5-单硝异山梨醇酯 ( 5-IM-C)为对照 ,进行国产 5-单硝异山梨醇酯 ( 5-IM-T)的药物动力学和相对生物利用度的研究。 1 2名男性健康志愿者 ,先后单剂量和多剂量随机交叉口服国产 5-IM 4 0 mg,用 GC-ECD测定其血药浓度 ,一室模型拟合或梯形法求药动学参数。多剂量连续 5d口服国产或进口胶囊 ,Tmax( h)为4 .75± 0 .4 5和 5.58± 1 .51 ,Cmax( μg/L)为 4 40 .68± 54.83和 4 51 .3 8± 8,MRT( h)为 1 1 .0 1± 0 .67和 1 1 .0 5± 0 .73 ,AUC0→∞ ( μg/L·h- 1 )为 5955.55± 689.83和 61 80 .65± 853 .0 4。其主要药物动学参数经方差分析 ,两者无显著差异 ( P>0 .0 5)。两种胶囊在服药 1 6h后 ,血药浓度降至产生耐受性的阈值浓度以下 ( <3 0 0μg/L )。两种胶囊体外溶出率 a%与相应时间的体内吸收分数 f均呈显著正相关 ( P<0 .0 5)。两种制剂稳态下的 FI分别为 1 .54± 0 .1 0和 1 .50± 0 .1 6。单剂量和多剂量下国产对进口胶囊的相对生物利用度分别为 97.4 2 %± 1 1 .79%和 97.1 6%± 1 0 .95%。两种胶囊药动学特点相似 ,具有生物等效性。更多还原

【Abstract】 To determine the pharmacokinetics and relative bioavailability of domestic and imported sustained release capsules of 5 isosorbide mononitrate(5 IM), twelve healthy male volunteers were given 5 IM following a single and multiple oral dose in an open randomized crossover study. The plasma levels of 5 IM were measured by gas chromatography with electron captured detector method. The paramaters such as T max , C max , MRT and AUC 0→∞ were calculated and there were no significant differences between the two kinds of capsules. The major pharmacokinetic parameters of domestic and imported 5 IM sustained release capsules with a 5d multiple dose were shown respectively as following: T max (h)4.75±0.45 and 5.58±1.51; C max (ng/ml)440.68±54.83 and \{451.38\}±88;MRT(h)11.01±0.67 and 11.05±0.73;AUC 0→∞ (ng/ml·h) 5955.55±689.83 and 6180.65±\{853.04.\} The fraction of drug absorbed \%in vivo\% was correlated well with the percentage amount of drug released in vitro at corresponding time (P<0.05),and the fluctuation indexes on the fifth day in multiple dose study were not significantly different between the two formulations (P>0.05).The relative bioavailability of the domestic capsules for single and multiple dose were 97.42%±11.79% and 97.16%±10.95%. Domestic 5 IM sustained release capsules showed bioequivalence compared with the imported capsules and provided the same nitrate low interval in the latter part of the 24 h dosing interval.更多还原