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甘地胶囊口服给药后四种活性成分在正常大鼠和糖尿病大鼠体内的比较药代动力学

Comparative pharmacokinetics of four active components on normal and diabetic rats after oral administration of Gandi capsules.

作者信息

Xu Renjie, Qi Jia, Zhan Ruan-Juan, Zhou Gui-Sheng, Hao Bin, Ma Jing, Wei Xin, Xu A-Jing, Zhang Jian

机构信息

Department of Pharmacy, Xinhua Hospital No. 1665 Kongjiang Road, Yangpu District Shanghai 200092 China

Department of Pharmacy, The First Affiliated Hospital, Wenzhou Medical University Wenzhou China.

出版信息

RSC Adv. 2018 Feb 9;8(12):6620-6628. doi: 10.1039/c7ra11420f. eCollection 2018 Feb 6.

Abstract

The Gandi capsule, a famous traditional Chinese medicine (TCM), is a hospital preparation that has been widely used in China for decades for the treatment of diabetes. The aim of this study is to compare the pharmacokinetics of four of the active components of Gandi capsules, which are the primary antidiabetic ingredients, on normal and diabetic Sprague-Dawley rats following oral administration of the capsules. Baicalin, wogonoside, wogonin, loganin and puerarin (internal standard) were prepared using methanol precipitation, and the separation of the five components was achieved through a ZORBAX Eclipse Plus C column by gradient elution using water (containing 0.1% formic acid) and acetonitrile as the mobile phase. After oral administration of Gandi capsules to the normal and diabetic rats, plasma was harvested and analyzed using liquid chromatography coupled with tandem mass spectrometry, and the primary pharmacokinetic parameters were calculated by DAS 2.0. Compared with the normal group, some pharmacokinetic parameters especially the AUC of the four compounds significantly increased in the diabetic groups. The results demonstrated that the four constituents in normal and diabetic rats had obvious differences in some pharmacokinetic characteristics, suggesting that the rate and extent of drug metabolism were altered in diabetic animals. The results could be helpful for demonstrating the compatibility mechanism and providing clinical medication guidance for Gandi capsules.

摘要

甘地胶囊是一种著名的中药,是一种医院制剂,在中国已广泛用于治疗糖尿病数十年。本研究的目的是比较甘地胶囊的四种活性成分(主要抗糖尿病成分)在正常和糖尿病Sprague-Dawley大鼠口服胶囊后的药代动力学。采用甲醇沉淀法制备黄芩苷、汉黄芩苷、汉黄芩素、马钱苷和葛根素(内标),以水(含0.1%甲酸)和乙腈为流动相,通过ZORBAX Eclipse Plus C柱梯度洗脱实现五种成分的分离。对正常和糖尿病大鼠口服甘地胶囊后,采集血浆并采用液相色谱-串联质谱法进行分析,用DAS 2.0计算主要药代动力学参数。与正常组相比,糖尿病组部分药代动力学参数尤其是四种化合物的AUC显著增加。结果表明,正常和糖尿病大鼠体内的四种成分在某些药代动力学特征上存在明显差异,提示糖尿病动物的药物代谢速率和程度发生了改变。该结果有助于阐明甘地胶囊的配伍机制,为临床用药提供指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c00/9078286/6f1d5240e681/c7ra11420f-f1.jpg

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