Pharmacokinetic Study of Caffeic and Rosmarinic Acids in Rats after Oral Administration

摘要

p-Coumaric and ferulic acid are actively taken up by monocarboxylic acid transporter(MCT),whereas gallic acid,caffeic acid(CA),and rosmarinic acid(RA)are absorbed by paracellular diffusion in human intestinal Caco-2 cells,although CA has low affinity for MCT.We previously demonstrated that p-coumaric acid has a much higher absorption efficiency than gallic acid in rats,owing to the MCT-mediated absorption of p-coumaric acid in vivo(J.Agric.Food Chem.2004,52,2527-2532).Here,absorption of orally administered CA and RA in rats has been studied to investigate their intestinal absorption characteristics and pharmacokinetics in vivo and to compare the results with those of p-coumaric and gallic acids obtained under identical conditions.Rats were given 100 mumol/kg body weight of CA and RA,and blood was collected from the portal vein and abdominal artery after administration.CA,RA,and their metabolites were quantified by a coulometric detection method using HPLC-ECD.The serum concentration of intact CA and RA in the portal vein peaked at 10 min after administration,with a C_(max)of 11.24 mumol/L for CA and 1.36 mumol/L for RA.The area under the curve(AUC)for intact CA and RA in the portal vein was calculated from the serum concentration-time profile to be 585.0 and 60.4 mumol min L~(-1),respectively.The absorption efficiency of CA was about 9.7-fold higher than that of RA.Overall,the absorption efficiency of these compounds in vivo increases in the order:gallic acid = RA < CA < p-coumaric acid,which is in good agreement with results obtained in Caco-2 cells in vitro.