Gemfibrozil is a widely used lipid modifying drug with well-established hypolipidemic and anti-atherosclerotic benefits; however, the presence of a carboxylic acid moiety in its structure is responsible for side effec...Gemfibrozil is a widely used lipid modifying drug with well-established hypolipidemic and anti-atherosclerotic benefits; however, the presence of a carboxylic acid moiety in its structure is responsible for side effects in the gastrointestinal tract. The principle of bioisosterism was applied to design derivatives replacing the carboxylic acid group. The carboxylic acid group was replaced with bioisoteric groups, such as 1,2,4-triazole-3-thiol and hydroxamic acid. The derivatives were then synthesized, characterized, and evaluated in rats for reduced gastrointestinal irritation and hypolipidemic effects. Gemfibrozil was used as standard for comparison. The derivatives demonstrated less gastric irritation and retained hypolipidemic effects, however the hypolipidemic affects were significantly less than that of Gemfibrozil. The results of this study offers a direction for further research on the application of bioisosterism for the design of new derivatives of Gemfibrozil and other fibric acid derivatives.展开更多
药品和个人护理品(Pharmaceuticals and personal care products,PPCPs)的环境危害及修复治理日益受到重视,为揭示满江红对含PPCPs生活污水的净化效果,以典型PPCPs吉非罗齐、卡马西平及满江红为供试材料,采用室内模拟培养试验,研究满江...药品和个人护理品(Pharmaceuticals and personal care products,PPCPs)的环境危害及修复治理日益受到重视,为揭示满江红对含PPCPs生活污水的净化效果,以典型PPCPs吉非罗齐、卡马西平及满江红为供试材料,采用室内模拟培养试验,研究满江红在不同培养时间(1、2、4、8 d)和不同PPCPs初始浓度(0、1、10、100、1000μg·L^(-1))生活污水中的生长状况,以及对常规污染物[氨氮(NH_(3)-N),硝态氮(NO_(3)-N),总磷(TP),化学需氧量(COD)]和PPCPs的去除率。结果表明,随着生活污水中PPCPs初始浓度的增加,满江红相对生长率及其耐受指数呈先增加后降低的趋势,且满江红在100、1000μg·L^(-1)PPCPs处理下生长受到抑制;与对照相比,1、10μg·L^(-1)PPCPs处理下满江红对氮、磷的去除效果显著增强(P<0.05),但100、1000μg·L^(-1)PPCPs处理下对氮、磷的去除效果显著减弱(P<0.05);在不同PPCPs初始浓度处理下,满江红对COD去除作用显著,且COD去除率随PPCPs初始浓度的增加而增加;满江红对吉非罗齐和卡马西平去除效果随培养时间的延长而增强,吉非罗齐去除率随PPCPs初始浓度的增加而增加(1000μg·L^(-1)PPCPs处理除外),而卡马西平去除率随PPCPs初始浓度的增加而降低。满江红对PPCPs有良好的去除效果,对生活污水中NH_(3)-N以外的常规污染物也有很好的去除能力,可作为含典型PPCPs生活污水的修复治理植物。展开更多
AIM: To develop a GC MS method for the study of pharmacokinetics of gemfibrozil in healthy human body. METHODS: A 25 m×0 2 mm ID HP 5 silica capillary column was used. The carrier gas was helium. The internal sta...AIM: To develop a GC MS method for the study of pharmacokinetics of gemfibrozil in healthy human body. METHODS: A 25 m×0 2 mm ID HP 5 silica capillary column was used. The carrier gas was helium. The internal standard was ibuprofen. After acidification with 3 mol·L -1 HCl solution, the plasma was extracted with n hexane — dichloromethane (3∶1) and then reacted with bis (trimethylsilyl) trifluoroacetamide (BSTFA). RESULTS: A good linearity was obtained from 0 4 to 60 0 μg·mL -1 of gemfibrozil in human plasma (γ=0 9992). The detection limit of gemfibrozil in plasma was 0 1 μg·mL -1 . The average recovery was 96 5%. The pharmacokinetics of gemfibrozil was determined by this GC MS method following a single oral dose of 600 mg gemfibrozil capsule given to each of 10 volunteers. The results showed that the plasma concentration time courses conformed to one compartment model. CONCLUSION: The established GC MS method was found to be a good method for determination of gemfibrozil in human plasma. The method was precise and sensitive.展开更多
文摘Gemfibrozil is a widely used lipid modifying drug with well-established hypolipidemic and anti-atherosclerotic benefits; however, the presence of a carboxylic acid moiety in its structure is responsible for side effects in the gastrointestinal tract. The principle of bioisosterism was applied to design derivatives replacing the carboxylic acid group. The carboxylic acid group was replaced with bioisoteric groups, such as 1,2,4-triazole-3-thiol and hydroxamic acid. The derivatives were then synthesized, characterized, and evaluated in rats for reduced gastrointestinal irritation and hypolipidemic effects. Gemfibrozil was used as standard for comparison. The derivatives demonstrated less gastric irritation and retained hypolipidemic effects, however the hypolipidemic affects were significantly less than that of Gemfibrozil. The results of this study offers a direction for further research on the application of bioisosterism for the design of new derivatives of Gemfibrozil and other fibric acid derivatives.
基金Project supported by the Program for New Century Excellent Talents in University （No. NCET-04-0651）, the National Natural Science Foundation of China （Nos. 20335030 and 20575036） and the Important Project of Natural Science Foundation of Shandong Province of China （No. Z2003B01）.
文摘药品和个人护理品(Pharmaceuticals and personal care products,PPCPs)的环境危害及修复治理日益受到重视,为揭示满江红对含PPCPs生活污水的净化效果,以典型PPCPs吉非罗齐、卡马西平及满江红为供试材料,采用室内模拟培养试验,研究满江红在不同培养时间(1、2、4、8 d)和不同PPCPs初始浓度(0、1、10、100、1000μg·L^(-1))生活污水中的生长状况,以及对常规污染物[氨氮(NH_(3)-N),硝态氮(NO_(3)-N),总磷(TP),化学需氧量(COD)]和PPCPs的去除率。结果表明,随着生活污水中PPCPs初始浓度的增加,满江红相对生长率及其耐受指数呈先增加后降低的趋势,且满江红在100、1000μg·L^(-1)PPCPs处理下生长受到抑制;与对照相比,1、10μg·L^(-1)PPCPs处理下满江红对氮、磷的去除效果显著增强(P<0.05),但100、1000μg·L^(-1)PPCPs处理下对氮、磷的去除效果显著减弱(P<0.05);在不同PPCPs初始浓度处理下,满江红对COD去除作用显著,且COD去除率随PPCPs初始浓度的增加而增加;满江红对吉非罗齐和卡马西平去除效果随培养时间的延长而增强,吉非罗齐去除率随PPCPs初始浓度的增加而增加(1000μg·L^(-1)PPCPs处理除外),而卡马西平去除率随PPCPs初始浓度的增加而降低。满江红对PPCPs有良好的去除效果,对生活污水中NH_(3)-N以外的常规污染物也有很好的去除能力,可作为含典型PPCPs生活污水的修复治理植物。
文摘AIM: To develop a GC MS method for the study of pharmacokinetics of gemfibrozil in healthy human body. METHODS: A 25 m×0 2 mm ID HP 5 silica capillary column was used. The carrier gas was helium. The internal standard was ibuprofen. After acidification with 3 mol·L -1 HCl solution, the plasma was extracted with n hexane — dichloromethane (3∶1) and then reacted with bis (trimethylsilyl) trifluoroacetamide (BSTFA). RESULTS: A good linearity was obtained from 0 4 to 60 0 μg·mL -1 of gemfibrozil in human plasma (γ=0 9992). The detection limit of gemfibrozil in plasma was 0 1 μg·mL -1 . The average recovery was 96 5%. The pharmacokinetics of gemfibrozil was determined by this GC MS method following a single oral dose of 600 mg gemfibrozil capsule given to each of 10 volunteers. The results showed that the plasma concentration time courses conformed to one compartment model. CONCLUSION: The established GC MS method was found to be a good method for determination of gemfibrozil in human plasma. The method was precise and sensitive.
