To the Editor.
—Drs Newman and Hulley1 review data from preclinical studies with lipid-lowering drugs, particularly fibrates and hydroxymethylglutaryl—coenzyme A (HMG-CoA) reductase inhibitors, and conclude that use of these drugs should be avoided except in patients at high short-term risk of CHD. However, the dose of gemfibrozil that produced hepatic adenomas was 10 mg/kg of body weight per day, whereas for lovastatin, hepatocellular carcinomas and adenomas were induced at a dose of 312 mg/kg per day but not at 62.5 mg/kg per day. Use of the area under the curve (AUC) is misleading because it provides no information on hepatic concentrations that, if the drugs are potentially hepatotoxic, would have more relevance than the AUC. In the absence of data on hepatic concentrations, I believe the dose expressed in milligrams per kiligrams of body weight per day is more reliable to assess potential toxicity than the AUC.Gemfibrozil is
Illingworth DR. Carcinogenicity of Lipid-Lowering Drugs. JAMA. 1996;275(19):1479–1480. doi:10.1001/jama.1996.03530430023026
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