Study On Absorption Mechanism And Pharmacokinetics Of Sinomenine

ObjectiveSinomenine is extracted from traditional Chinese crude drug--Sinenium acutum,which is used for therapy of beriberoid disease and rheumatoid disease. Sinomenine applicated widespeadly in clinic,main effects of it are anti-inflammatory,immune suppression, analgesia, depressurization, anti-arhythmia, resisting addiction of morphine, and so on.In the present study, Sinomenine needs long-term oral generally in clinic, and has short half-life, low bioavailability, might generate the drugs interaction when combined with other drugs.In this study, we investigated the absorption mechanism and pharmacokinetics of sinomenine and its extract, evaluated by the combination model of absorption and metabolism.These findings help to understand the dynamic process of Sinomenine in vivo.Furthermore,the reasons of low bioavailability was investigated,being beneficial to the development of the original plant. Meanwhile, the work could provide valuable data for drug permeability, absorption and bioavailability of forecasting calculation methods and models, being beneficial to explore to improve the theory and research methods for bioavailability.Materials and MethodsIn this paper, concentration of drugs in the perfusion fluid and plasma samples was determined by HPLC to study the absorption and pharmacokinetics of sinomenine; Single pass perfusion model was used to compare the Intestinal absorption characteristics of sinomenine and its extract sinomenine. To compare pharmacokineics of Puerarin and crude extract in rats. Nomal rats and liver fibrosis rats received sinomenine and sinomenine crude extract by oral administration respectively. The pharmacokinetics parameters were calculated with DAS 2.0.Their pharmacokinetic parameters were compared by SPSS 16.0.Results and Conclusions1. SPIP model can be used for investigation of absorption for sinomenine. Sinomenine, belonging to high permeability drug, have a good absorption in four segments (P>0.05). Concentration have a significant effect on Peff of sinomenine (P<0.05), the absorption mechanism was active transportion.Adding P-gp inhibitor verapamil hydrochloride, Peff in Jejunum intestinal was increased significantly, which indicating that sinomenine may be P-gp substrate. complex composition in extract have a significant effect on intestinal absorption of sinomenine.2. The accuracy, precision, sensitivity, specificity and linearity of HPLC method satisfied the requirement of pharmaceutical analysis.Pharmacokinetics of sinomenine and extract was significant difference after intragastric administration in rat (P<0.05),and Pharmacokinetics of sinomenine was significant difference after intragastric administration in liver fibrosis rat(P<0.05),compared with normal rats.