Preliminary Study On The Characters Of The Absorption And Metabolism Of Isosteviol Sodium By Intragastric And Intraduodenal Administration In Rats

Isosteviol?ent-16-ketobeyeran-19-oic acid?is a beyerane diterpene obtained by acid hydrolysis of stevioside.Recent studies show that it has good pharmacological activity in treating the hyperglycemia,cardiovascular disease and cancer.In order to increase its solubility researchers have changed its form into isosteviol sodium.However very less pharmacokinetics study of oral delivered isosteviol or isosteviol sodium has been done.In this article,we mainly investigate: 1)The solubility of isosteviol sodium at four different pH values.2)The two delivery ways were considered to study the PK parameters of isosteviol sodium in male rats: intragastric administration,intragastric co-administation of aluminum hydroxide with isosteviol and 3)The PK parameters of isosteviol sodium in rats through the intraduodenal administration and intravenous administration.4)Studying the absorption of isosteviol by everted gut model isolated from rats.The details are as follows:First part: according to phase solubility analysis method in the United States Pharmacopoeia,we use four pH values?pH = 2.0,6.0,7.4 and 9.0?of initial solutions in in vitro studies.We detect the solubility of isosteviol sodium,at pH=2.0,we find that the low concentration of isosteviol sodium?1mg·m L-1³mg·m L-1?is insoluble,existing in the form of molecule,which is a better situation of absorption in stomachs.While at other pH values,the low concentration of isosteviol sodium,existing in the form of ion,which is a better situation of absorption in intestines.So the pH value would not be the constrains of absoption in stomachs and intestines of rats at low concentration of isosteviol sodium.Second part: wese studied the PK parameters of isosteviol sodium in male rats by two drug-delivery ways: intragastric administration,intragastric co-administation of aluminum hydroxide with isosteviol(1mg·kg^-1).We deal with the concentrations of isosteviol in rat plasma from 0 to 24 h by statistical analysis,we concluded that comparing the intragastric administration with the co-adiministration,the co-adiministration made the maximum time?Tmax?ahead of time,and the area under concentration?AUC?reduced in the male rats.Third part: from statistical analysis we found out that the PK parameters of isosteviol sodium through intraduodenal administration and intravenous administration(1mg·kg^-1)has difference between the male and female rats.Comparing the intraduodenal administration with the intragastric one,the AUC and half-time of the male rats didn't show any difference.The Tmax of the male rats showed no difference while the C_max had the same result.Forth part:for further study of the absorption of isosteviol sodium via the intestinal,we used the rat everted gut sac model,with the concentration of isosteviol sodium was 50 ?g·mL-1.The samples were acquired from 0 4 h,we handled the data of sample concentrations through statistical analysis,and concluded that the absorption amount of isosteviol sodium by the duodenum,jejunum,ileum and colon showed no difference.