Effect of formula compatibility on the pharmacokinetics of components from Dachengqi Decoction (大承气汤) in rats

Abstract

Objective

To investigate the effect of prescription compatibility on the pharmacokinetics of components from Dachengqi Decoction (DCQD, 大承气汤) in rats.

Methods

Twenty-four male rats were randomly and equally divided into the DCQD group, Dahuang (Radix et Rhizoma Rhei, Polygonaceae) group, Houpo (Magnolia officinalis Rehd., Magnoliaceae) group, and Zhishi (Fructus Aurantii Immaturus, Rutaceae) group. The blood samples were collected before dosing and subsequently at 10, 15, 20, 30, 45 min, 1, 2, 4, 8, and 12 h following gavage. The levels of aloe-emodin, rhein, emodin, chrysophanol, honokiol, magnolol, hesperidin, and naringin in rat serum were quantified using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for pharmacokinetic study.

Results

The area under the curve (AUC), mean retention time (MRT), the peak concentration (C_max) of aloe-emodin, rhein, emodin, and chrysophanol in the DCQD group were significantly different compared with the Dahuang group (P <0.05, respectively). The mean plasma concentration, C_max, and the absorption of Dahuang’s component in the DCQD group were obviously lower at each time point than those in the Dahuang group, while the elimination process of Dahuang’s component was obviously delayed (P <0.05). Half-lives of aloe-emodin, chrysophanol, and rhein were also extended in the DCQD group (P <0.05, respectively). In the DCQD group, the mean plasma concentration, AUC, C_max and absorption of honokiol, and magnolol were significantly lower (P <0.01, respectively) at each time point than those in the Houpo group, while the drug distribution half-life time (T_1/2α), the drug eliminated half-life time (T_1/2β), MRT, and time of peak concentration (T_max) were significantly delayed (P <0.05, respectively). Pharmacokinetic parameters of hesperidin and naringin in the Zhishi group were not significantly different as compared with the DCQD group (P >0.05, respectively), while the MRT of naringin was significantly longer.

Conclusions

The compatibility in Chinese medicine could affect the drug’s pharmacokinetics in DCQD, which proves that the prescription compatibility principle of Chinese medicine formulations has its own pharmacokinetic basis.