盐酸多奈哌齐鼻用温敏凝胶在大鼠脑组织内药动学与药效学相关性

Correlation between pharmacokinetics and pharmacodynamics of donepezil hydrochloride thermosensitive nasal gel in rat brain tissues

目的研究盐酸多奈哌齐鼻用温敏凝胶在大鼠脑组织内药动学与药效学相关性。方法大鼠经鼻腔给予盐酸多奈哌齐鼻用温敏凝胶后,分别在不同时间处死动物,分离全脑组织、称定并匀浆。采用HPLC法测定脑组织中药物浓度,采用紫外分光光度法测定脑组织中乙酰胆碱酯酶(AchE)的活性,绘制脑组织中药物浓度-时间-AchE活性变化曲线并对药物浓度与AchE活性的相关性进行分析。结果给药10 min后,在大鼠脑组织中盐酸多奈哌齐的浓度达峰值,AchE的活性达最小值;AchE活性与药物浓度呈同步变化,两者间存在明显负相关。且药物效应与脑组织中药物浓度之间不存在滞后现象。结论盐酸多奈哌齐鼻用温敏凝胶在大鼠脑组织内药动学与药效学之间存在显著相关性。

Objective To determine the correlation between pharmacokinetics and pharmacodynamics of donepezil hydrochloride thermosensitive nasal gel in the brain tissues of rats.Methods Rats were sacrificed at different time after nasal administration of the donepezil hydrochloride nasal gel and the whole brain tissues of each rat were separated and weighted before the homogenization.The concentration of donepezil hydrochloride in the brain homogenates was determined by HPLC method.Meanwhile,the activity of acetylcholinesterase(AchE)in the brain homogenates was analyzed by UV method.Finally,drug concentration and AchE activity in brain tissues were plotted against time and the correlation between them was estimated.Results The maximal concentration of donepezil hydrochloride and minimal activity of AchE in the brain tissues both reached 10 min after the administration of nasal gel.The concentration of donepezil hydrochloride and the activity of AchE in the brain tissues changed synchronously with obvious negative correlation between them.In addition,no lag-time phenomenon was found between AchE-inhibiting effect and donepezil hydrochloride concentration in the brain tissues.Conclusion A significant correlation between pharmacokinetics and pharmacodynamics of donepezil hydrochloride thermosensitive nasal gel may exist in rat brain tissues.