The Studies On The Pharmacokinetic, Absorption Properties And Distributed Properties Of Cinnamic Acid In Rats

Objective：To study the pharmacokinetic, absorption properties and distributed propertiesof cinnamic acid in rats.Methods：Based on the LC-MS-MS method, the absolute bioavailability（Fabs） wascalculated by measuring the plasma concentration after iv or ig administration ofcinnamic acid in rats; Based on the One-way Intestinal Perfusion Rat Model, theabsorption rate constant （Ka） and the apparent absorption coefficient （Peff） in eachintestinal section were obtained to study absorption kinetics of cinnamon acidabsorption mechanism and the effect about Transporter protein, the absorption rateconstants （Ka） and apparent absorption coefficient （Peff） of cinnamic acid in threedifferent region（duodenum, jejunum and ileum）of rat intestine were evaluated by threedifferent concentrations, research transporter protein cinnamic acid absorption, theduodenum as Pgp protein investigated bowel, and the jejunum as MRP2investigationbowel; Then, the in situ vascularly perfused intestine preparation was used toinvestigate the intestinal absorption rate, and to assesse the model, the absorptioncapacity of three different concentrations of cinnamic acid was evaluated in situ theenterohepatic vascular perfusion model; The tissue distribution of cinnamicwas investigated.Result：Pharmacokinetic parameters after ig: t_max=0.50±0.08h; t_1/2β=0.41±0.09h; CL=5.58±0.48; MRT_{0â†'∞}=0.56±0.16h; AUC_{0â†'∞}=868.74±186.48ng·h·mL^-1, Pharmacokineticparameters after iv: t_1/2β=0.34±0.06h; CL=2.94±1.25L·h^-1·kg^-1; MRT_{0â†'∞}=0.35±0.07h;AUC0â†'t=1071.20±130.09ng·h·mL^-1. Fabs=81.10%.The absorption rate constants（Ka） and apparent absorption coefficient （Peff） of cinnamic acid in three different region ofrat intestine were in the following sequence; duodenum>jejunum>ileum. The value ofKa and Peff in the duodenum was signifcantly lower than in other intestinal sections（P<0.05）, The Ka and Peff of different drug concentration had no significant influence.The Ka and Peff of cinnamic acid were no significantly increased by indomethacin injejunum, but they were significantly increased by verapamil hydrochloride induodenum. the intestinal absorption rate in the situ vascularly perfused intestinepreparation was80%,85%,83%to High dose group, Middle dose group and Lowdose group, respectively. The tissue distribution and excretion studies show that thereare litter cinnamic acid in heart, brain and lungs. the cinnamic acid can be detected inthe urine.Conclusion: The results demonstrated that cinnamic acid was well absorbed, it was quicklydistributed, and eliminated; the duodenum and jejunum were most importantabsorption sites; Its absorption mechanism may be related to passive diffusion. It maybe the substrate of P-gp, not but MRP2; Eliminate of cinnamic acid in rats is fast,and itis not easy to enrich, beside, its excretion is need by renal.