The Pharmacokinetics Of The Five Anthraquinones In Rats

Rheum is one of the traditional Chinese medicine in clinical treatment, which has Clearing Heat Antitoxicant, Blood-Activating Stasis-Removing, Sterilization blood pressure and other effects. Pharmacokinetics is to study the relation of existence place in vivo, quantity and time after medication and to explain the mathematical relationship of these dynamic laws. The main matter which play efficacy is anthraquinone compounds, mainly including Aloe-emodin, Rhein, Emodin, Chyrsophanol and Physcion etc. The pharmacokinetic mainly research the Absorption, Distribution, Metabolism and Excretion process of drugs in the animal body. Drug contents of biological samples are very low, purification, enrichment and determination of the biological samples is the key problems to pharmacokinetics in traditional Chinese medicine. To establish a method for determination of the Five Anthraquinones (Aloe-emodin, Rhein, Emodin, Chyrsophanol and Physcion) in rats plasma by solid-phase extraction-high performance liquid chromatography internal standard method, and study the Absorption, Distribution, Excretion and the Plasma Protein Binding Rate process of the drug with the proposed method, these studies provide a reference of the rational clinical application of rhubarb in vivo. Studies are as follows:1. Simultaneous determination and pharmacokinetics of the Five Anthraquinones in rat plasma after oral administration by SPE-HPLC method. By comparison of different preprocessing systems and optimization of chromatograph conditions, the SPE-HPLC method to determinate the concentration of drugs was set. The study provides a reference for parmacokinetics analysis of the Five Anthraquinones in rats. Using a DAS 2.1.1 pharmacokinetics program, the pharmacokinetic parameters were calculated. By comparing the Primary Pharmacokinetic Parameters between the cerebral ischemia model group and normal rats.The results were indicated:after the mixed Rhubarb aglycone at the does of 300 mg/kg were given to rats by intragastric administration, pharmacokinetic model of Aloe-emodin, Rhein, Emodin, Chyrsophanol and Physcion were fitted to one-compartment, two-compartment, two-compartment, one-compartment, two-compartment models respectively in normal rats, but in the cerebral ischemia model group the Five Anthraquinones are two-compartment models, and they are widely distributed in the body. The Cmax were 0.04160 and 0.1943,0.4008 and 0.7331,0.2019 and 0.3492,0.06994 and 0.1050, 0.1936 and 0.2018μg/mL in the normal and cerebral ischemia model group rats. The model group, with a high value in Cmax, it is showed that the cerebral ischemia model group rats are better in absorption of the Five Anthraquinones.2. Determination of the Plasma Protein Binding Rate of the Five Anthraquinones by SPE-HPLC. The plasma balance dialysis was used, an SPE-HPLC for the quantitative determination of the Five Anthraquinones was presented and used to calculate the protein binding rate in plasma of rat. The average protein binding rate is 93.1%,91.3%,95.2%,87.5% and 89.6% for Aloe-emodin, Rhein, Emodin, Chrysophanol and Physcion in plasma, it is showed that there were high protein binding rate in plasma.3. Determination of the Five Anthraquinones in rat tissues by a optimal SPE-HPLC method. The study provides a reference for tissue distribution of the Five Anthraquinones. The results were indicated:the Five Anthraquinones were widely distribution in the rats body, and they eliminated slowly in rat tissues, especially in kidney.4. Excretion studies on the Five Anthraquinones in rats by SPE-HPLC. By optimizing the conditions of different preprocessing systems, to estimate the excretion of the Five Anthraquinones in dung and urine, Draw their mean cumulative excretion and excretion rate curves. The results were showed that:the excretion rate of the Five Anthraquinones are largest in dung and urine within 8-12 h. The cumulative amount of Aloe-modin, Rhein, Emodin, Chyrsophanol and Physcion reached to 10.1%,3.10%,30.3%,18.9% and 19.2% of the dose in dung within 140 h, and the cumulative amount reached to 0.52%,0.19%,0.12%,0.063% and 0.060 % of the dose in urine within 140 h.This paper established the SPE-HPLC internal standard method for the determination of the Five Anthraquinones. With a further investigation on Absorption, Distribution, Excretion and the Plasma Protein Binding Rate of the Five Anthraquinones, it will lay a foundation for the pharmacodynamics of the Rheum, and it also can be used for the study on the toxicology and clinical rational use of drugs.