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Gemfibrozil. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in dyslipidaemia.


PMID 3056692

Abstract

Gemfibrozil is a lipid-regulating agent which is generically classified as a fibric acid derivative, but which exhibits different pharmacological effects from other such drugs. Published data indicate that in patients with all types of dyslipidaemia (except type I) gemfibrozil 800 to 1200 mg/day is particularly effective in reducing total plasma triglyceride concentrations. The reduction in total plasma cholesterol is statistically significant with the most pronounced response occurring in patients with severe hypercholesterolaemia. Gemfibrozil also effectively increases high density lipoprotein cholesterol. In a 5-year double-blind prospective placebo-controlled study in over 4000 male patients with types IIa, IIb and IV primary dyslipidaemia (but without coronary symptoms), gemfibrozil 600mg twice daily significantly reduced the incidence of cardiac events (by 34%) compared with placebo, although overall mortality was not affected. In comparative studies with clofibrate similar reductions in plasma lipid levels have been observed, although these changes tend to be more favorable overall with gemfibrozil. Gastrointestinal symptoms and rash are the only side effects produced more frequently with gemfibrozil than with placebo. Although gemfibrozil is hepatotoxic in male rats, drug-induced pathological liver changes have not been reported in humans. Thus, gemfibrozil is an effective drug indicated for the treatment of severe hypertriglyceridaemia, and in certain patients with severe hypercholesterolaemia who are unresponsive to other standard therapies. In addition, it would appear to reduce the risk of cardiac events in patients with dyslipidaemia, although its effects on overall mortality remain speculative.