药学学报, 2019, 54(11): 2064-2068
引用本文:
王恩莹, 金成婷, 王俊俊, 陈勇, 韩凤梅. 冰片对大鼠体内长春西汀药动学的影响[J]. 药学学报, 2019, 54(11): 2064-2068.
WANG En-ying, JIN Cheng-ting, WANG Jun-jun, CHEN Yong, HAN Feng-mei. Effects of borneol on the pharmacokinetics of vinpocetine in rats[J]. Acta Pharmaceutica Sinica, 2019, 54(11): 2064-2068.

冰片对大鼠体内长春西汀药动学的影响
王恩莹, 金成婷, 王俊俊, 陈勇, 韩凤梅
湖北大学中药生物技术省重点实验室, 药物高通量筛选技术国家地方联合工程研究中心, 湖北 武汉 430062
摘要:
长春西汀(vinpocetine,VP)被广泛应用于脑血管功能障碍和神经损伤的治疗,而传统中药冰片(borneol,BN)常用于促进治疗中枢神经系统疾病的药物的吸收与分布。本文旨在研究BN对VP药动学和组织分布的影响。健康SD大鼠随机分成3组,分别灌胃VP(10 mg·kg-1)、VP+BN(10 mg·kg-1+150mg·kg-1)及VP+BN(10 mg·kg-1+75 mg·kg-1)进行药动学研究。另设两组分别灌胃VP(10 mg·kg-1)及VP+BN(10 mg·kg-1+150mg·kg-1)进行组织分布研究。动物实验经湖北大学伦理委员会批准,遵循实验动物管理条例的规定。采用LC-MS/MS法检测血浆及组织中VP的浓度,计算其药动学参数。与VP单用组相比,高剂量联合用药组VP的AUC0-∞、MRT0-∞t1/2z分别显著提高1.98、1.22和1.42倍;肝、肾、脑组织暴露量分别增加1.5、1.5和1.3倍。联合使用BN和VP有助于改善VP平均驻留时间短、口服生物利用度低、脑暴露低等不良药动学特征。
关键词:    长春西汀      冰片      药动学      组织分布     
Effects of borneol on the pharmacokinetics of vinpocetine in rats
WANG En-ying, JIN Cheng-ting, WANG Jun-jun, CHEN Yong, HAN Feng-mei
Hubei Province Key Laboratory of Biotechnology of Traditional Chinese Medicine, National&Local Joint Engineering Research Center of High-throughput Drug Screening Technology, Hubei University, Wuhan 430062, China
Abstract:
Vinpocetine (VP) has been widely used to treat cerebrovascular disorders and nerve injury. Borneol (BN), as an important traditional Chinese medicine, is commonly used to promote the absorption and distribution of central nervous system drugs. In this work, a LC-MS/MS method was developed to determine the level of VP in rat plasma and tissues, and to evaluate the effect of co-administration of BN with VP by oral gavage on the absorption and tissue distribution of VP in rats. Rats were divided into VP (10 mg·kg-1), VP (10 mg·kg-1) + BN (75 mg·kg-1) and VP (10 mg·kg-1) + BN (150 mg·kg-1) groups for pharmacokinetic study, and divided into VP (10 mg·kg-1) and VP (10 mg·kg-1) + BN (150 mg·kg-1) groups for tissue distribution study. The animal experiment was approved by Ethics Committee of Hubei University, and complied with the guideline for caring and using of laboratory animals. Compared to VP group, the AUC0-∞, MRT0-∞ and t1/2z of VP + BN (150 mg·kg-1) group increased significantly, by 1.98-, 1.22- and 1.42-fold respectively, and the exposure in plasma, liver, kidney and brain increased by 2-, 1.5-, 1.5- and 1.3-fold respectively. The pharmacokinetic results suggested that co-administration of BN with VP is beneficial for overcoming the undesirable pharmacokinetic characteristics of VP, such as short residence time, low oral bioavailability and brain exposure in clinical usage.
Key words:    vinpocetine    borneol    pharmacokinetics    tissue distribution   
收稿日期: 2019-04-28
DOI: 10.16438/j.0513-4870.2019-0339
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