Effects Of Pharmaceutical Excipients On The Intestinal Absorption Of Fosinopril Sodium

H⁺/peptide cotransporter （Pept1） mainly located in the intestinal brush bordermembrane and depends on the [H⁺], it can transport dipeptide or tripetide or substratesinto the cells. It plays an important role in the absorption and bioavailability of oraldrugs. The factors which can influence the transport fuction, expression of Pept1orthe affinity of Pept1with substrate drugs also can change the intestinal absorption ofdrugs. Pharmaceutical excipients can affect the activity of trasporters and enzymes.Excipients may change the absorption and efficacy of oral drugs. Therefore, it is anew idea to enhance the oral absorption of substrate drugs by using excipients whichcan up-regulated the activity of Pept1.Fosinopril was selected as a model drug, because it has a high affinity with Pept1.We evaluated the effects of different concentrations excipients （PEGs, acrylic resins,poloxamer188, carbomer934P） on the intestinal absorption of Fosinopril sodium bysingle-pass intestinal perfusion in SD rats. The results showed that the Fosinoprilsodium was mainly absorbed in the promixal small intestine （duodenum and jejunum）,and minor in distal small intestine （ileum）. Pharmaceutical excipients had differenteffects on the Fosinopril sodium in the rats of different small intestinal segments.PEG400-0.2%could increase the absorption of Fosinopril sodium in ileumsignificantly, PEG400-0.5%also increased the absorption of the drug in jejunum（p<0.05）. But the absorption of Fosinopril sodium in three intestinal segements weresignificantly inhibited by F68-0.5%（p<0.05）. In the jejunum, Eudragit L100-0.1%,L100-55-0.1%, L100-55-0.2%had an obvious effects on promoting the absorption ofFosinopril sodium （p<0.05）. In duodenum, Eudragit L100-55-0.1%,L100-55-0.2%had an obvious promoting effect on the absorption of model drug. Carbomer934P（concentraton range0.1-0.5%） could increase the intestinal absorption of the drug induodenum and jejunum, and carbomer-0.5%could promote the absorption of drug inileum significantly （p<0.05）. And the lower pH of perfusate enhanced the intestinalabsorption of Fosinopril sodium in different segments of rat intestine. The lower concentration Gly-Sar can increase the absorption of Fosinopril sodium, however thehigh concentration reduced the absorption. In the basis of single-pass intestinalperfusion in SD rats. Eudagit L100, L100-55, Carbomer934P were selected furtherfor pharmacokinetic trial in rats. The results showed that those excipients can improvethe absorption of fosinoprilat which is the active metabolite of fosinopril sodium.Compared to the control group, the AUC_0-t, AUC_0-∞and C_max of fosinoprilat wereincreased significantly （p<0.05）; T_max was slightly increased too.The results of this thesis showed that types and concentrations of pharmaceuticalexcipients could influence the absorption of Fosinopril sodium. These results couldprovide some data and theoretical support for the rational design of formulations andprescription of substrates of Pept1. At the same time, it was the basis of the furtherstudy on the interactions of excipients and Pept1.