论文部分内容阅读
本文研究了影响酒石酸卡巴拉汀鼻腔吸收的因素,考察了其体内药代动力学行为并评价了其脑靶向性。采用大鼠在体鼻腔循环法研究酒石酸卡巴拉汀浓度和药液p H值对药物鼻腔吸收的影响;大鼠静脉注射及鼻腔给药后,采用高效液相色谱(high performance liquid chromatography,HPLC)法测定血浆及脑组织中药物浓度,并计算药动学参数、脑靶向指数(drug targeting index,DTI)和药物鼻脑直接转运百分比(nose-to-brain direct transport percentage,DTP)。研究表明,酒石酸卡巴拉汀在鼻腔内的吸收机制为被动扩散,p H 6.0时药物吸收速率常数最大。该药物鼻腔给药的绝对生物利用度为73.58%。与静脉注射相比,鼻腔给药后药物入脑更加迅速,在脑组织的分布显著增加,DTI为静脉注射的195.27%。鼻腔给药后约48.79%药物可从鼻腔通道直接转运至脑部而未经全身血液循环,显著提高了药物的入脑速度和程度。同时,与静脉注射相比,酒石酸卡巴拉汀在脑部的清除半衰期延长了1.4倍。综上,酒石酸卡巴拉汀鼻腔给药不仅可有效促进药物的吸收,而且能显著加快药物的入脑速度和增强药物的脑组织分布,更有利于中枢神经系统疾病的治疗。
In this paper, the factors that affect the nasal absorption of rivastigranate-loaded rivastigmine were investigated, and their pharmacokinetic behavior in vivo and their brain targeting were evaluated. Rat nasal circulation method was used to study the effect of rivastigmine tartrate concentration and drug p H value on intranasal absorption. After high-performance liquid chromatography (HPLC) Method was used to determine the concentration of drug in plasma and brain tissue. Pharmacokinetic parameters, drug targeting index (DTI) and nose-to-brain direct transport percentage (DTP) were calculated. Studies have shown that the rivastigmine tartrate absorption mechanism in the nasal cavity is passive diffusion, and the drug absorption rate constant is the highest at p H 6.0. The drug’s nasal administration of the absolute bioavailability of 73.58%. Compared with intravenous injection, nasal administration of drugs into the brain more rapidly, the distribution of brain tissue increased significantly, DTI intravenous injection of 195.27%. Approximately 48.79% of the drug can be directly transported from the nasal passage to the brain after nasal administration without systemic blood circulation, which significantly improves the rate and extent of brain penetration into the brain. At the same time, rivastigmine tartrate showed a 1.4-fold longer half-life in the brain than intravenous injection. In conclusion, intranasal administration of rivastigmine tartrate can not only effectively promote the absorption of drugs, but also significantly accelerate the drug into the brain and enhance the brain tissue distribution of drugs, which is more conducive to the treatment of central nervous system diseases.