The supramolecular interaction of gemfibrozil with β-cyclodextrin （β-CD） was studied by spectrofluorimetry. The mechanism of the inclusion was discussed by spectrofluoremetry, infrared spectrum and ^1H NMR spectru...The supramolecular interaction of gemfibrozil with β-cyclodextrin （β-CD） was studied by spectrofluorimetry. The mechanism of the inclusion was discussed by spectrofluoremetry, infrared spectrum and ^1H NMR spectrum. The results showed that a 1 ： 1 （β-CD ： gemfibrozil） complex was formed with an apparent association constant of 3.844 × 10^3 L·mol^-1. Based on the enhancement of the fluorescent intensity of gemfibrozil, a spectrofluorimetric method for the determination of gemfibrozil in bulk aqueous solution in the presence of β-CD was developed. The linear range was 3.30 ng·mL^- 1 -6.00 ug·mL^-1 with the detection limit of 0.980 ng·mL^-1. There was no interference from the excipients normally used in tablet composition and the serum main compositions. The proposed method was then successfully applied to the determination of gemfibrozil in capsules and serum.展开更多
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
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
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The supramolecular interaction of gemfibrozil with β-cyclodextrin （β-CD） was studied by spectrofluorimetry. The mechanism of the inclusion was discussed by spectrofluoremetry, infrared spectrum and ^1H NMR spectrum. The results showed that a 1 ： 1 （β-CD ： gemfibrozil） complex was formed with an apparent association constant of 3.844 × 10^3 L·mol^-1. Based on the enhancement of the fluorescent intensity of gemfibrozil, a spectrofluorimetric method for the determination of gemfibrozil in bulk aqueous solution in the presence of β-CD was developed. The linear range was 3.30 ng·mL^- 1 -6.00 ug·mL^-1 with the detection limit of 0.980 ng·mL^-1. There was no interference from the excipients normally used in tablet composition and the serum main compositions. The proposed method was then successfully applied to the determination of gemfibrozil in capsules and serum.
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.
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.
