Studies On Pharmacokinetics Of Palmatine And Jatrorrhizine In Huangteng In Rats

Huangteng is a dry cane of the Fibraurea recisa Pierre.It also has the function of clearing away heat and toxic substances,purging fire and easing constipation.The main active ingredients of Huangteng are alkaloids,in which,the palmatine and jatrorrhizine are representative.At present,the preparation of palmatine is mainly used for the treatment of various infectious diseases in clinical practice,and has definite curative effect and high safety.The significant inhibitory effect on acetylcholinesterase activity in vitro of palmatine was first discovered in our team,and its activity is 50 times stronger than the positive control drug of donepezil,the research results have been granted the national patent for invention.At present,the palmatine preparations are all six kinds of preparations,and our research group plans to develop them as five new drugs for the resistance to Alzheimer’s disease.It is necessary to carry out in-depth pharmacokinetic studies on the total alkaloids of Huangteng.However,there are few pharmacokinetic studies on the total alkaloids extracted from the Huangteng.Therefore,the pharmacokinetics of total alkaloids were studied using the palmatine and the jatrorrhizine as the index components.The experiment content and results are as follows:1.Studies on absorption and oral bioavailability of palmatine and jatrorrhizine in Huangteng in ratsIn our present study,the total alkaloids of Huangteng were given to the rats by intragastric and tail vein administration.The concentration of palmatine and jatrorrhizine in the plasma of rats were also determined by HPLC.Pharmacokinetic parameters and oral bioavailability were calculated by 3P97 software.The main pharmacokinetic parameters were determined as follows:for the intragastric group,the C_max of palmatine and jatrorrhizine were（0.91±0.06）and（0.70±0.08）mg·L^-1;T_max of palmatine and jatrorrhizine were（35.24±0.83）and（47.76±1.24）min;T_1/2 of palmatine and jatrorrhizine were（187.03±1.53）and（105.64±16.99）min,AUC of palmatine and jatrorrhizine were（280.30±18.69）and（144.36±1.06）μg·min·mL^-1;for the intravenous group,the T_1/2 of palmatine and jatrorrhizine were（172.18±12.38）and（147.26±1.82）min;AUC of palmatine and jatrorrhizine were（2553.14±214.91）and（328.83±10.81）μg·min·mL^-1.The oral bioavailability of palmatine was 10.98%and jatrorrhizine was 43.90%.2.Studies on the absorption properties of palmatine and jatrorrhizine in Huangteng in rat’s intestinal eversion modelIn our present study,rat’s intestinal eversion model was established.The absorption of drug in duodenum,jejunum and ileum of rats were measured by HPLC.Absorption rate parameters were calculated to analyze the effects of palmatine and jatrorrhizine in different intestinal tracts.The results showed that different doses of total alkaloids of Huangteng were absorbed linearly in each of the intestinal tracts.The absorption of palmatine was absorbed passively in vivo;the absorption of jatrorrhizine in the body was a combination of passive absorption and active transport.The experimental results of different segments of the intestine showed that the absorption tendency of the intestinal components in different concentrations of flavescens was jejunum>ileum>duodenum;jatrorrhizine was ileum>jejunum>duodenum.3.Studies on the distribution of palmatine and jatrorrhizine in Huangteng after intragastric administration in ratsIn our present study,the total alkaloids of Huangteng were administered by intragastric method,and the distribution of palmatine and jatrorrhizine in various tissues were also investigated.The results of HPLC showed that palmatine and jatrorrhizine were widely distributed in rats.The concentration of palmatine was higher in stomach,small intestine and liver,followed by lung and kidney,and less in brain,spleen and heart.The concentration of jatrorrhizine was higher in stomach,small intestine and liver,followed by lung and brain,and less in kidney,heart and spleen.Oral administration requires an absorption process.The content of the palmatine and jatrorrhizine measured at the 0.5 h,1 h,2 h and 3 h time points were basically the same in the different tissues of the rats and showing an increase and then decreased trend.4.Studies on the excretion of palmatine and jatrorrhizine in Huangteng in ratsIn our present study,the excretion characteristics were studied after intragastric administration of total alkaloids of Huangteng in rats,and the bile was collected after intragastric administration 36 h,and the urine and feces were collected within 72 h,and bilobalide,urine,faeces and radixanthin were examined by HPLC in rats,and the cumulative excretion,excretion rate and the excretion rate were all calculated.The results showed that palmatine and jatrorrhizine in the bile accumulation excretion were（259.25±9.02）,（258.78±19.93）μg,accumulated excretion rate were（2.67±0.10）,（19.60±1.35）%,the excretion rate were（7.20±0.25）,（7.18±0.49）μg·h^-1;and the urine accumulation excretion were（37.36±0.86）,（57.87±4.84）μg,accumulated excretion were（0.38±0.01）,（4.38±0.37）%,the excretion rate were（0.52±0.01）,（0.80±0.07）μg·h^-1;and the fecal accumulated excretion were（4956.13±88.82）,（737.62±27.72）μg,accumulated excretion rate were（50.99±0.91）,（55.88±2.10）%,the excretion rate were（68.84±1.23）,（10.24±0.39）μg·h^-1.The excretion of palmatine and jatrorrhizine were mainly fecal excretion.