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Summary Inclusion complexation between dimethyl-β-cyclodextrin and a very poorly water-soluble serum lipid-regulating agent, gemfibrozil, was studied. Products were prepared by several methods (physical mixing, kneading, spray-drying and ultrasonic treatment) in four different molecular ratios (2:1, 1:1, 1:2 and 1:3). The possibility of complex formation between the drug and the host molecule was studied by thermal analysis. Supplementary techniques, such as Fourier transformation-infrared spectroscopy and X-ray diffractometry, were also applied to interpret the results of thermal study of the products.

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Relationships between R M values and mobile phase composition have been examined for six fibrate-type drugs — bezafibrate, ciprofibrate, clofibrate, clofibric acid, fenofibrate, and gemfibrozil. They were separated in horizontal chambers on RP18 plates by use of mobile phases containing phosphate buffer and different amounts of six modifiers — acetone, acetonitrile, dioxane, isopropanol, methanol, and tetrahydrofuran. Plates were visualized under UV irradiation at λ = 254 nm, and scanned with a densitometer in multi-wavelength scan mode. Optimum modifier concentrations were also investigated on RP8 and CN plates for comparison. The linearity of relationships between R M and modifier volume fraction, molar fraction, and the logarithm of the molar fraction was calculated. Most results fitted the Snyder-Soczewiński equation with r > 0.95; for almost half r > 0.99. Separation of all the drugs was achieved on RP18 plates with mobile phase containing 70% dioxane in pH 7.60 phosphate buffer.

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Relationships between R M values and mobile phase composition have been determined for the six antihyperlipidemic agents-bezafibrate, ciprofibrate, clofibrate, clofibric acid, fenofibrate, and gemfibrozil. The drugs were separated on silica gel, CN, and Diol plates using mobile phases containing n -hexane as weakly polar diluent and five polar modifiers: acetone, dioxane, ethyl methyl ketone, ethyl acetate, and tetrahydrofuran. The optimum mobile phases were also investigated on alumina, NH 2 , and polyamide phases for comparison. The linearity of relationships between R M and modifier volume fraction, molar fraction, and logarithm of molar fraction was calculated. Plates were developed in horizontal chambers, visualized under UV irradiation at λ = 254 nm, and scanned with a densitometer in the multi-wavelength scan mode. Most results fitted the Snyder-Soczewinski equation with r > 0.9; for approximately half r > 0.99. Separation of all the drugs was achieved on Diol plates with mobile phases containing 20–30% of each modifier in n -hexane, and with hexane-acetone, 9 + 1, on CN plates. Five drugs were separated using the same mobile phases on silica gel. The best separation was obtained on Diol plates with tetrahydrofuran-hexane, 2 + 8, as mobile phase.

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101 1773 1779 Fujii S, Sobel BE: Direct effects of gemfibrozil on the fibrinolytic system. Diminution of synthesis of plasminogen activator inhibitor

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.3 Fluoxetine 1987 8.1 16.8 11.7 7.3 5.7 Gemfibrozil 1981 5

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.: Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial. JAMA, 2001, 285 , 1585–1591. Wittes J. T. Relation of gemfibrozil

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339 341 Tal, A., Rajeshawari, M., Isley, W.: Rhabdomyolysis associated with simvastatin-gemfibrozil therapy. South Med. J., 1997, 90 , 546

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R. P. Byrd Jr 2001 Simvastatin-diltiazem drug interaction resulting in rhabdomyolysis and hepatitis Tenn. Med. 94 339 – 341 . [18]. A. Tal M. Rajeshawari W. Isley 1997 Rhabdomyolysis associated with simvastatin-gemfibrozil

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151 174 Rubins, H. B., Robins, S. J., Collins, D. és mtsai: Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high

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Basaranogly, M., Acbay, O., Sonsuz, A.: A controlled trial of gemfibrozil in the treatment of patients with nonalcoholic steatohepatitis. J. Hepatol., 1999, 31 , 384. Sonsuz A. A

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