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The Study Of Pharmacokinetics Of Naringin And Its Intestinal Absorption In Rats

Posted on:2010-12-20Degree:MasterType:Thesis
Country:ChinaCandidate:L SuFull Text:PDF
GTID:2144360275960026Subject:Integrative basis
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Naringin is a kind of flavanone,which is one production from Secondary Metabolites of Citrus(Rutaceae).Some researches show that,Naringin possesses strong biological activities on reducing blood lipid,sedation,antioxidation,antitumor,antifungal, anti-atherosclerosis,ect.In addition,naringin can increase the bioavailability of some oral drugs,because of its effect of competitive inhibition with drug metabolizing enzymes. Based upon the goog biological activity,in this study,using the HPLC to detect the naringin in rats,run the pharmacokinetics and the absorption mechanism on rats' intestine.1.A pharmacokinetics of naringin in rats(1).Determination of naringin in biosamplesA sensitive method for the determination of naringin in rats' biosamples was developed and validated after solid-phase extraction.The chromatographic separation was achieved on a reversed-phase Phenomenex LUNA 5u C18(2) 100A,(4.6×150mm,5μm) column with the mobile phase of methanol:water:36%acetic acid(45:55:3.3),pH=2.5, flow rate 1.0mL·min-1,and the analyties were detected by using UV detector at 283nm.The results showed that the endogenous of biosamples did not interfere with the determination of biosamples.A good linear relationship was obtained in the different concentration ranges(r>r>0.9905);The intra-day accuracy ranged from 9.50%11.14% and the inter-day accuracy ranged from 9.50%11.14%.Average extraction recoveries ranged from 100.81%109.55%.This method was successfully applied to the pharmacokinetics studies on rats.(2).The pharmacokinetics of naringin in ratsThe study of pharmacokinetic was performed after single oral dose.The plasma concentration of naringin was analyzed by HPLC and plasma concentration-time data may be described with a open two compartmental pharmacokinetic model using PKsolution 2.0 to estimate the pharmacokinetic parameters. The results showed that the blood concentration - time curve of naringin can be described as the two-compartment model,rapidly distributed and then eliminated from rats.From the pharmacokinetic parameters can be seen that after 10min of dosing the drugs can be detected in the blood,Tmax was 1.2h,Cmax was 728.00ng/mL,t1/2(β)was 3.952h.(3).Tissue distribution of naringin in ratsAfter single oral dosing of naringin(0.32g·kg-1),then rats were sacrificed by decapitation at 15min,60min,105min,180min and 720min pose-dose,respectively. Removed tissues and organs such as the heart,liver,spleen,kidney,lung,stomach, duodenum,brain,fat,muscle,skin,testis,ovary rapidly,and homogenized the tissues. Then determined as the method described above.The results showed that after oral administration,the naringin underwent a rapid wide distribution in the tissues throughout the whole body within the time course.In general,as the time elapsed,the concentrations of naringin rapid decreased in each tissue.The highest concentrations of naringin were found in the stomach,followed by the duodenum,kidney and liver.These results were very similar with the pharmacokinetic property of naringin.2.The absorption mechanism of naringin in the rats' intestine(1).Determination of naringin in biosamples of rats' intestineA sensitive method for the determination of naringin in the test solution biosamples was developed,and the samples was extracted by solid-phase extraction(SPE).The chromatographic separation was achieved on a reversed-phase Phenomenex LUNA 5u C18(2) 100A,(4.6×150mm,5μm) column with the mobile phase of methanol:water:36%acetic acid(45:55:3.3),pH=2.5,flow rate 1.0mL·min-1,column temperature:room temperature,detection wavelength:283nm.The results showed that the endogenous of biosamples did not interfere with the determination of biosamples.A good linear relationship was obtained in the concentration range of 0.1μg·mL-1~10.0μg.mL-1(r>0.9997);The intra-day accuracy ranged from 7.60%~10.03%and the inter-day accuracy ranged from 7.72%~8.86%.Average extraction recoveries ranged from 80.31%~98.58%.This method was successfully applied to the study of the absorption mechanism of naringin in the rats' intestine.(2).The absorption mechanism of naringin in the rats' intestineUsing the everted small intestine model,determinated absorbing activities in rats' jejunal and ileal with different concentrations of naringin,while observed the absorption which impacted by naringin solutions which added verapamil,one kind of P-gp inhibitors, and Polysorbate-80.The results showed that,when the concentration was from 20μg·mL-1 to 120μg·mL-1, the uptake of naringin increased linearly and did not appear to be saturated.There wasn't significant difference in the permeability coefficient between the jejunum and ileum at low concentration,but the latter was higher than the former at high concentration. Verapamil showed effect on increasing the absorption of naringin remarkably,and Tween-80 enhanced the absorption of naringin in jejunum only.
Keywords/Search Tags:Naringin, Pharmacokinetics, absorption mechanism
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