Treatment of combined hyperlipidemia with fluvastatin and gemfibrozil, alone or in combination, does not induce muscle damage.
Although combination therapy using 3-hydroxy-3-methylglutaryl coenzyme A (HMG-Co-A) reductase inhibitors and fibrates is efficacious in combined hyperlipidemia, such treatment has been associated with myopathy. For this reason, we studied the effects of fluvastatin and gemfibrozil, alone or in combination, on muscle. A total of 21 patients with combined hyperlipidemia were recruited who were matched for age, body mass index, and baseline levels of total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides, creatine phosphokinase, and myoglobin. Patients were randomized to three groups for 6-week treatment with fluvastatin at 40 mg/day, gemfibrozil at 600 mg twice daily, or a combination of the two drugs. Parameters for muscle damage were rises in levels of serum creatine phosphokinase and myoglobin compared with pre-exercise levels; these were assessed 1 hr and 8 hr after a 45 min lean body mass standardized ergometer test, which was performed before and after treatment in all patients. Biopsies from the quadriceps muscle were taken 48 hr after each test. Fluvastatin lowered total cholesterol and LDL-C by 23% and 35%, respectively (p < 0.01), with no effects on triglycerides and HDL-C. Gemfibrozil lowered triglycerides by 40% (p < 0.01) but did not lower total cholesterol or LDL-C significantly. The combination therapy decreased total cholesterol, LDL-C, and triglycerides by 28%, 29%, and 39%, respectively (p < 0.05). Pre-exercise creatine phosphokinase and myoglobin levels were not affected by treatment in any group.(ABSTRACT TRUNCATED AT 250 WORDS)
Smit
J W
JW
Department of Internal Medicine, University Hospital of Utrecht, The Netherlands.
Jansen
G H
GH
de Bruin
T W
TW
Erkelens
D W
DW
D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001706:Biopsy; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D004311:Double-Blind Method; D004338:Drug Combinations; D005080:Exercise Test; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D015248:Gemfibrozil / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000008:administration & dosage / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006949:Hyperlipidemias / Q000145:classification / Q000188:drug therapy*; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D009211:Myoglobin / Q000097:blood; D010919:Placebos; D011446:Prospective Studies; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004338:Drug Combinations; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D009211:Myoglobin; D010919:Placebos; D014280:Triglycerides; D000077340:Fluvastatin; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D003402:Creatine Kinase; D015248:Gemfibrozil