In an attempt to elucidate the mechanisms underlying retinoid-induced hyperlipidemia, the effects of etretinate (Tigason) and isotretinoin (Roaccutane) on two different plasma fat elimination variables and on the plasma fatty acid composition were studied. Twelve patients with various hyperkeratotic disorders participated in a double-blind cross-over study of etretinate and isotretinoin. Each drug was given for 8 weeks with an 8-week intermission. On five occasions an intravenous fat tolerance test (IVFTT) was performed and the lipoprotein lipase activity (LPLA) in adipose tissue and skeletal muscle was measured. Isotretinoin significantly reduced the fat elimination rate as measured by IVFTT (p less than 0.001) and also decreased the muscle LPLA (p less than 0.05). The etretinate-induced depression of these variables was not statistically significant. The LPLA of adipose tissue and the plasma fatty acid composition were not markedly altered by any of the drugs. The observed changes are probably not sufficient to entirely explain retinoid-induced hyperlipidemia but the results strengthen the opinion that plasma lipid metabolism is more unfavourably affected by isotretinoin than etretinate.
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