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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。
The 5-mononoisosorbide ester (5-IM-C) was used as a control to study the pharmacokinetics and relative bioavailability of 5-mononoisosorbinate (5-IM-T) Twelve male healthy volunteers were randomized to receive domestic 5-IM 4 0 mg at randomized crossover doses. The plasma concentrations were determined by GC-ECD, and pharmacokinetic parameters were determined by one-compartment model fitting or trapezoidal method. Multi-dose oral 5d domestic or imported capsules, Tmax (h) of 4.75 ± 0.54 and 5.58 ± 1.51, Cmax (μg / L) of 4 40.68 ± 54.83 and 4 51.38 ± 8, MRT (h) was 11.01 ± 0.67 and 1 1 .0 5 ± 0.73, and AUC0 → ∞ (μg / L · h-1) were 5955.55 ± 689.83 and 61 80 .65 ± 853 .0 4. The main pharmacokinetic parameters were analyzed by ANOVA, there was no significant difference (P> 0.05). After taking the drugs for 16 h, the plasma concentrations of the two capsules dropped to below the threshold level of tolerance (<300 μg / L). The in vitro dissolution rates of two kinds of capsules showed a significant positive correlation with the body absorption fraction f at the corresponding time (P <0.05). The FIs at steady state for the two formulations were 1.54 ± 0.10 and 1.50 ± 0.16, respectively. The relative bioavailability of domestic capsules to imported capsules at single and multiple doses were 97.4 ± 11.79% and 97.1 ± 10.95%, respectively. The two capsules have similar pharmacokinetic characteristics and bioequivalence.