PHARMACOKINETICS OF THE COMBINATION OF FLUVASTATIN AND GEMFIBROZIL

High-risk patients with dyslipidemias resistant to diet and single-age nt pharmacotherapy may require combination therapy to achieve target l evels of low density lipoprotein, triglycerides, and high density lipo protein. Combinations of fibrates and 3-hydroxy-3-methylglutaryl-coenz yme A reductase inhibitors are effective, but because of safety concer ns related to myopathy and rhabdomyolysis, it is important to consider the possibility of pharmacokinetic interactions when such combination s are used. In this study, the area under the curve, maximum plasma co ncentration, acid time to maximum concentration for fluvastatin and ge mfibrozil are compared, when used alone and in combination, in patient s 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 flu vastatin 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 ma ximum concentration when comparing the combination with each drug alon e. These pharmacokinetic data add support to the clinical observations that the combination of fluvastatin and gemfibrozil is both effective and safe.