Abstract
High-risk patients with dyslipidemias resistant to diet and single-agent pharmacotherapy may require combination therapy to achieve target levels of low density lipoprotein, triglycerides, and high density lipoprotein. Combinations of fibrates and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors are effective, but because of safety concerns related to myopathy and rhabdomyolysis, it is important to consider the possibility of pharmacokinetic interactions when such combinations are used. In this study, the area under the curve, maximum plasma concentration, and time to maximum concentration for fluvastatin and gemfibrozil are compared, when used alone and in combination, in patients with hyperlipidemia and either coronary or carotid atherosclerosis, or a family history of coronary artery disease. A total of 17 patients were studied in a random sequence, open-label, crossover study of fluvastatin at 20 mg twice daily, gemfibrozil at 600 mg twice daily, and the combination of the 2 drugs. No significant difference was observed in area under the curve, maximum plasma concentration, and time to maximum concentration when comparing the combination with each drug alone. These pharmacokinetic data add support to the clinical observations that the combination of fluvastatin and gemfibrozil is both effective and safe.
Publication types
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Clinical Trial
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Comparative Study
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Randomized Controlled Trial
MeSH terms
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Anticholesteremic Agents / administration & dosage
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Anticholesteremic Agents / pharmacokinetics*
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Anticholesteremic Agents / therapeutic use
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Arteriosclerosis / blood
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Arteriosclerosis / complications
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Carotid Stenosis / blood
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Carotid Stenosis / complications
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Coronary Artery Disease / blood
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Coronary Artery Disease / complications
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Coronary Disease / blood
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Coronary Disease / genetics
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Cross-Over Studies
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Drug Combinations
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Fatty Acids, Monounsaturated / administration & dosage
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Fatty Acids, Monounsaturated / pharmacokinetics*
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Fatty Acids, Monounsaturated / therapeutic use
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Female
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Fluvastatin
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Gemfibrozil / administration & dosage
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Gemfibrozil / pharmacokinetics*
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Gemfibrozil / therapeutic use
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Humans
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Hydroxymethylglutaryl CoA Reductases / administration & dosage
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Hydroxymethylglutaryl CoA Reductases / pharmacokinetics*
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Hydroxymethylglutaryl CoA Reductases / therapeutic use
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Hydroxymethylglutaryl-CoA Reductase Inhibitors*
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Hyperlipidemias / drug therapy*
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Indoles / administration & dosage
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Indoles / pharmacokinetics*
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Indoles / therapeutic use
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Lipoproteins, HDL / blood
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Lipoproteins, LDL / blood
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Male
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Middle Aged
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Pilot Projects
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Placebos
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Safety
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Triglycerides / blood
Substances
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Anticholesteremic Agents
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Drug Combinations
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Fatty Acids, Monounsaturated
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Indoles
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Lipoproteins, HDL
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Lipoproteins, LDL
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Placebos
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Triglycerides
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Fluvastatin
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Hydroxymethylglutaryl CoA Reductases
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Gemfibrozil