氯苄律定CPU-86017在小鼠静脉给药和脑室给药后通过血脑屏障的渗透性(英文)

Permeability of CPU-86017 through the BBB after Intravenous and Intracerebroventricular Injection in Mice

目的 :研究小鼠静脉给药和脑室给药后CPU 86 0 17通过血脑屏障的双向渗透性。方法 :小鼠给予 3 0mg/kgCPU 86 0 17(盐酸对氯苄四氢小檗碱 )后 ,在 5 ,10 ,2 0 ,30 ,6 0min时用HPLC测脑、心、肾和血中CPU 86 0 17的水平。结果 :两种途径给药的CPU 86 0 17在小鼠脑 ,心、肾和血浆中的最大浓度基本上在 10min时都达到最大值 ,在静脉给药组分别为 0 83±0 335 ,2 5 13± 4 17,5 6 0± 19 6 9,2 2 3± 0 97μg/ml,在脑室给药组分别为 2 3 6 8± 4 2 ,15 9± 10 2 4 ,7 93± 4 6 8,3 32± 2 3μg/ml。小鼠血浆浓度很快减少。静脉给药后CPU 86 0 17在肾中的最大浓度是 5 6 0± 19 6 9μg/g ,脑室给药后 ,在脑中的最大浓度是2 3 6 8± 4 2 μg/g。静脉给药 6 0min后 ,CPU 86 0 17在肾中和脑中的浓度没有显著性差异。脑室给药后 ,CPU 86 0 17到达外周组织和血浆中的浓度每 5分钟都会有变化 ,而静脉给药后 ,在 2 0 ,30和 6 0min时 ,脑中的药物浓度仍不能被检测出。结论 :CPU 86 0 17通过血脑屏障的渗透可以通过两条途径 :从血液循环到脑和从脑到全身循环。然而 ,这两条途径存在很大的不同。从血渗透到脑比从脑渗透到外周更困难。

AIM:To investigate the bi-directional penetration of CPU-86017 across the BBB (Blood Brain Barrier) following iv and icv (intracerebroventricular) administration in mice.METHOD:The levels of CPU-86017 (p-Chlorobenzyltetrahydroberberine hydrochloride) in the brain, heart, kidney and blood of mice after acute administration of 3.0 mg/kg of CPU-86017 were measured by validated HPLC assay at several time points: 5, 10, 20, 30 and 60 minutes. RESULT:The maximum concentrations of CPU-86017 in the brain, heart, kidney and plasma achieved at 10 minutes by both routes of administration were 0.83±0.335, 25.13±4.17, 56.0±19.69, and 2.23±0.97 μg/ml in the iv group and 23.68±4.2,15.9±10.24, 7.93±4.68 and 3.32±2.3 μg/ml in the icv group, respectively. The decline in concentrations was rapid in plasma. The highest concentration of CPU-86017 was found in the kidney (56.0±19.69 μg/g) after iv administration and in the brain (23.68±4.2 μg/g) after icv injection. The difference in concentrations in the kidney and heart was not significant at 60 min after iv administration. Given by icv administration CPU-86017 reached the peripheral tissues and plasma at each of the five time points, whereas by the iv route at 20, 30 and 60 min the drug could not be detected in the brain.CONCLUSION:The permeability of CPU-86017 through the BBB was well established by two ways: blood circulation to the brain and brain to general circulation. However, a big difference exists between these ways. It is more difficult to penetrate from the blood to the brain than from brain to the peripheral.