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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。
OBJECTIVE: To study the bidirectional permeability of CPU 86 0 17 through the blood-brain barrier after intravenous and intraventricular administration in mice. Methods: The mice were given 300 mg / kg CPU 86 0 17 (paracetamol hydrochloride), and the brain, heart, kidney and blood CPU were measured by HPLC at 5, 10, 20, 30 and 60 minutes The level of 86 0 17. Results: The maximum concentration of CPU 86 0 17 administered by both routes in mice brain, heart, kidney and plasma reached a maximum at 10 min basically. In the intravenous administration group, the maximum concentration was 0 83 ± 0 335, 2 5 13 ± 4 17,5 6 0 ± 19 6 9,2 2 3 ± 0 97μg / ml in the intraventricular administration group were 23 6 8 ± 4 2, 15 9 ± 10 2 4, 7 93 ± 4 6 8, 32 ± 2 3 μg / ml. Mouse plasma concentration decreased rapidly. After intravenous administration, the maximum concentration of CPU 86 0 17 in the kidney was 5600 ± 19 69 μg / g and the maximum concentration in the brain after intraventricular administration was 2368 ± 42 2 μg / g. After 60 min of intravenous administration, the concentration of CPU 86 0 17 in the kidney and in the brain was not significantly different. After intracerebroventricular administration, the concentration of CPU 86 0 17 arriving in peripheral tissues and plasma varied every 5 minutes, and drug concentrations in the brain at 20, 30, and 60 min after intravenous administration were still undetectable . Conclusion: The penetration of the CPU 86 0 17 through the blood-brain barrier can take place in two ways: circulating blood from the brain to the brain and from the brain to the systemic circulation. However, there is a big difference between the two approaches. Permeation from the blood to the brain is more difficult than from the brain to the periphery.