Study on integrated PK/PD of rhubarb in the treatment of yang-deficiency constipation model rats
10.16438/j.0513-4870.2017-1075
- VernacularTitle:大黄治疗阳虚便秘模型大鼠的整合PK/PD研究
- Author:
Xiao-hong GONG
1
;
Yi-meng ZHOU
1
;
Li ZHENG
1
;
Yun-qiu TANG
1
;
Li-hong GONG
1
;
Lin-yuan YU
1
;
Yun-xia LI
1
;
Cheng PENG
1
Author Information
1. State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources Co-founded by Sichuan Province and MOST/The Ministry of Education Key Laboratory of Standardization of Chinese Herbal, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
rhubarb;
pharmacokinetics;
pharmacodynamics;
principal component analysis;
integration of pharmacokinetics/pharmacodynamics
- From:
Acta Pharmaceutica Sinica
2018;53(4):561-566
- CountryChina
- Language:Chinese
-
Abstract:
Study on the integrated pharmacokinetics/pharmacodynamics (PK/PD) model of rhubarb in rats with yang-deficiency constipation based on the principle of traditional Chinese medicine system. The rat model of yang-deficiency constipation was established using vinegar and ice water containing activated carbon. The blood samples with 0.5 mL were collected from orbital venous plexus at 0, 5, 10, 15, 30, 60, 120, 240, 480, 720, 1 440 min time points after oral administration of rhubarb decoction, and the dosage is equivalent to crude drug 2.5 g·kg-1. The concentration of aloe-emodin, rhein, emodin and chrysophanol in rat plasma were determined by HPLC, and ELISA method was used to detect the activities of motilin (MTL), gastrin (GT), endothelin (ET) and vasoactive intestinal peptide (VIP) at different time points in serum. SPSS 21.0 software was used for analysis of component correlation and principal component, and WinNonlin 6.30 software was used to fit PK/PD model. Compared with the pharmacokinetic parameters of normal rats, in addition to emodin in the model rats showed characteristics of good absorption and slow to elimination; the content of MTL in model rats was significantly lower than that in normal rats. The composite values of the concentration and effect obtained by principal component analysis were connected by Sigmoid-Emax model. We established the integrated PK/PD model of rhubarb in treating yang-deficiency constipation to provide a new research direction for the material basis and mechanism of rhubarb treatment of yang deficiency constipation.