Effect Of Aurantii Fructus Immaturus And Citri Reticulatae Pericarpium On The Pharmacokinetics Of Omeprazole In Rats And The Reasons On Chemical Components

ObjectiveThe purpose of this paper is to study the effect of qi regulating drugs, such as Aurantii Fructus Immaturus and Citri Reticulatae Pericarpium, on the pharmacokinetics of omeprazole in rats and find the reasons on chemical components.Methods1. The concentration of synephrine in Aurantii Fructus Immaturus and hesperidin in Citri Reticulatae Pericarpium were detecting by high performance liquid chromatography according to the method of Chinese Pharmacopoeia2010. The concentration of synephrine, hesperidin, naringin, rutin and quercetin in Aurantii Fructus Immaturus decoction (AFID), Citri Reticulatae Pericarpium decoction (CRPD) and grapefruit juice (GFJ) were detecting by HPLC.2. The compounds of AFID, CRPD and GFJ were identified by LC-MS.3. The method for the determination of omerpazole in rat’s plasma by HPLC was established.4. The rats were orally administered AFID2g/(kg·d), CRPD2g/(kg·d), GFJ20mL/(kg·d) and water20mL/(kg·d) for28days, respectively. The rats were orally administered omeprazole at29th day. The blood samples were collected at different time points. The concentration of omerprazole in plasma was detected by HPLC. The pharmacokinetic parameters were calculated through Kinetica5.0.Results1. The concentration of synephrine in Aurantii Fructus Immaturus was0.32%. The concentration of hesperidin in Citri Reticulatae Pericarpium was3.63%. The concentration of synephrine and hesperidin in AFID were2.54mg/g and1.56mg/g. The concentration of synephrine and hesperidin in CRPD were2.70mg/g and2.39mg/g. The concentration of hesperidin and naringin in GFJ were4.19μg/mL and290.62μg/mL.2. There are42,34and38kinds of compounds in AFID. CRPD and GFJ were detected by HPLC-MS, respectively.8compounds were both in AFID and GFJ, while10compounds were both in CRPD and GFJ.3. A sensitive and reliable HPLC detection assay was established for the concentration-determination of omeprazole in rat plasma.4. Compared to the blank group, CL of AFID group, CRPD group and GFJ group ws reduced; Cmax and AUC were increased.Conclusion1. AFID, CRPD and GFJ improved the plasma concentration of omeprazole in rats.2. AFID, CRPD and GFJ inhibited elimination kinetic process of omeprazole in rats.3. Naringin and bergamottin may be the material basis of interaction between AFID and omeprazole.4. Naringin and6,7-dihydroxy bergamottin may be the material basis of interaction between CRPD and omeprazole.