低分子海藻酸钾降压作用及药动学的实验研究  

Antihypertensive Effect and Pharmacokinetics of Low Molecular Mass Potassium Alginate

作　　者：冀为[1] 陈欲云[1] 杜俊蓉[1] 喻冬柯[1] 郑晓媛[1] 杨芳[1] 于传兴 李德山 赵长义 乔奎蕴 

机构地区：[1]四川大学华西药学院药理学与生物制药系,成都610041 [2]大连雅威特生物工程有限公司技术研发中心

出　　处：《四川大学学报（医学版）》2009年第4期694-696,703,共4页Journal of Sichuan University(Medical Sciences)

摘　　要：目的研究低分子海藻酸钾对自发性高血压大鼠(SHRs)血压的影响及其在小鼠体内的药动学规律。方法采用尾脉搏间接测压法测定SHRs收缩压,40只大鼠随机分为5组:空白溶媒对照组、氢氯噻嗪片剂组(6.25mg/kg)、低分子海藻酸钾高剂量、中剂量和低剂量组(500、250、100mg/kg),每天灌胃给药,连续给药28d;每周测量血压,并观察停药后3d、6d的血压变化。KM种小鼠灌服3H-低分子海藻酸钾100mg/kg(74MBq/kg),分别于给药后2、5、10、20、30min以及1、2、4、6、12、24、48、72、96、120、144h尾部取血,测定样品放射性活性,经DAS2.0软件拟合低分子海藻酸钾口服给药在小鼠体内的药动学参数。结果与同期溶媒对照组比较,连续给药21d和28d,氢氯噻嗪和低分子海藻酸钾3个剂量组的SHRs血压水平均降低(P<0.01);停药3d和6d时,6.25mg/kg氢氯噻嗪的降压作用消失(P>0.05);在停药3d时,低分子海藻酸钾高、中、低3个剂量组的收缩压均低于同期溶媒对照组(P<0.05或P<0.01);停药6d时,250及500mg/kg低分子海藻酸钾仍可降低SHRs血压水平(P<0.01)。低分子海藻酸钾灌胃给药后在小鼠体内药动学规律符合二室模型,吸收相半衰期为2.76h,分布相半衰期为42.30h,消除相半衰期为42.31h,体内半衰期为36.28h。结论低分子海藻酸钾连续口服给药可剂量依赖性地降低SHRs血压,且停药6d仍呈现持续的降压作用,这可能与低分子海藻酸钾口服给药后体内消除缓慢有关。Objective To investigate the effect of low molecular weight potassium alginate （L-PA） on blood pressures in spontaneously hypertensive rats （SHRs） and its pharmaeokineties characteristics in mice. Methods The systolic blood pressure （SBP） was measured by tail-cuff method in conscious SHRs. Forty rats were randomly assigned to the following five groups： control, hydrochlorothiazide （HCT, 6.25 mg/kg）, L-PA in low, middle or high dose groups （100, 250, 500 mg/kg）. SHRs were intragastrieally （i. g. ） administrated once daily for 28 days. The SBP was measured once weekly during drug treatment, and 3 and 6 days after drug with drawal. KM mice were i.g. administered with 100 mg/kg （74 MBq/kg） of 3 H-L-PA. Tenμ1 blood samples were obtained from the tail vein at 2, 5, 10, 20, 30 rain and 1, 2, 4, 6, 12, 24, 48, 72, 96, 120 or 144 h after drug administration for measuring radioactivities. Pharmaeokinetics parameters of the oral administration of L-PA were analysed with DAS 2.0 software. Results Twenty-one or 28 days after administration, the rats in the groups treated with HCT or LPA at 100, 250 or 500 mg/kg had a significant decrease in SBP （P〈0. 01 vs control group）. Three or 6 days after drug withdrawal, the antihypertensive effect of HCT disappeared （P〉0.05）, whereas the rats treated with 250 or 500 mg/kg L-PA still had lower SBP than the controls （P〈0.01）. The L-PA at a dose of 100 mg/kg also led to a significant decrease in SBP 3 days after drug withdrawal （P〈0.05）. The pharmaeokineties of L-PA （i. g. ） was consistent with a two-compartment model, with 2.76 h of absorption half-life （t1/2 Ka）, 42.30 h of distributional half-life （t1/2α）, 42.31 h of elimination half-life （t1/2β）, and 36.28 h of terminal phase elimination half-life （t1/2z）. Conclusion Oral administration of L-PA has significant anti-hypertensive effect, which can be maintained to 6 clays after drug withdrawal. The sustaining anti-hypertensive effect of L-PA is probably associa

关 键 词：海藻酸钾 药动学 自发性高血压大鼠 降压作用 

分 类 号：R96[医药卫生—药理学]