| OBJECTIVE Swertiamatin is a representative and abundant active constituent ofSwertia species, the systematic studies on the in vivo pharmacokinetics ofswertiamarin was carried out in rats for the purpose of elucidating the metabolicprofile of swertiamarin, and providing the referred information for further researchand development on it.METHODS (1) using SPE as the sample clean-up procedure, development andvalidation of a LC-MS/MS method for the quantification of swertiamarin in biologicalsample. After oral administration of20,50mg/kg and intravenous administration of4mg/kg to rats, a non-compartmental model was employed to calculate the parameters,the parameters and bioavailability were calculated for each subject by the DAS2.0software.(2) After oral administration of20mg/kg to rats, the urine and feces werecollected in different period. Calculation of accumulative excretion amount ofswertiamarin in urine and feces within48hours, as well as calculating theaccumulative excretion amount in the percentage of totally administration amount.(3)Tissue distribution of swertiamarin in rats after oral administration was studied. Ratswere serially euthanized by spondylopathy luxation at different time points, andtissues such as liver, heart, spleen, lung, kidney and brain were taken out and madeinto homogenates preparation with physiological saline.(4) To compare thepharmacokinetics of swertiamarin in rats after oral administration of swertiamarin(20mg/kg) of swertiamarin alone and Qingyedan tablet.RESULT (1) The result of the method validation was showed that the method wasapplicable to biological samples for the pharmacokinetic study. After oraladministration of20,50mg/kg and intravenous administration of4mg/kg to rats, thefollowing parameters were obtained (mean): Tmax:0.95,1,0h, respectively; T1/2:1.10,1.21,1.05h, respectively; Cmax:1920.1,3950.49,7391.5μg/L, respectively; AUC0–∞:3593.7,8177.03,7321.0μg/L·h, respectively. Low absolute bioavailability, F%=9.8%.(2) It was shown that after a single oral administration of20mg/kg to rats, theaccumulative excretion amount of swertiamarin by the unchanged drug form were1%in urine, and0.05%in feces.(3) For the first time study on the tissue distribution ofswertiamarin in rats. swertiamarin was rapidly, extensively distributed to the variousrat tissues after oral administration of50mg/kg, time to reach maximum tissuesconcentration was1h. In the time to Tmax, the concentration of swertiamarin in the tissues was that kidney>liver>lung>spleen>heart>brain. The concentration ofswertiamarin in the tissues was not high and it’s hard to penetration into theblood–brain barrier. The results indicated that swertiamarin was rapidly eliminatedfrom the tissues, the tissue concentration of swertiamarin obviously declined in3hafter oral administration, and after12h, it could not find swertiamarin in tissues.(4) Incomparison with swertiamarin given alone, many parameters of swertiamarinpharmacokinetics, including AUC, CLz and Cmax, differed significantly（P<0.05）fromco-administration. Preliminary results indicate that the oleanolic acid may affectes thepharmacokinetics of the swertiamarin.Conclusion Development and validation of a LC-MS/MS method for thequantification of swertiamarin in biological samples. For the first time obtained thepharmacokinetic properties of swertiamarin in rats. It is showed that swertiamarin wasrapidly absorbed into the circulation system and rapidly eliminated from the tissues.Furthermore, the absolute bioavailability is low, and swertiamarin is hard topenetration into the blood-brain barrier, excreted by the unchanged drug from theurine and feces were low; marked variability in pharmacokinetics were exsisted afteradministration of swertiamarin alone and tablet. The pharmacokinetic parametersdetermined in this study will help guide design of dosing in future studies. |
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