国产5-单硝异山梨醇酯缓释胶囊在正常人体的药物动力学和相对生物利用度研究  

Pharmacokinetics and Relative Bioavailability of Domestic Sustained Release Capsules of 5 Isosorbide Mononitrate in Healthy Volunteers

作　　者：李嵘[1] 沈建平[2] 李梦秋 邱俊 丁红彬[2] 张银娣[2] 彭建和[3] 于爱琴 盛龙生[3] 

机构地区：[1]南京医科大学附属南京儿童医院,南京210008 [2]南京医科大学临床药理研究所,南京210029 [3]中国药科大学分析计算中心,南京210009

出　　处：《中国药科大学学报》2000年第4期273-277,共5页Journal of China Pharmaceutical University

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。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.

关 键 词：单硝异山梨醇酯 药物动力学 胶囊 生物等效性 

分 类 号：R96[医药卫生—药理学]