Gemfibrozil increases both apo A-I and apo E concentrations. Comparison to other lipid regulators in cholesterol-fed rats.
HDL cholesterol (HDL-C) was increased by gemfibrozil (+3.6-fold), fenofibrate (+1.3-fold) and ciprofibrate (+1.2-fold) but not clofibrate or bezafibrate when dosed PO at 50 mg/kg for 2 weeks in cholesterol-fed rats. Cholesterol in apo B-containing lipoproteins decreased with gemfibrozil (-76%), clofibrate (-12%) and ciprofibrate (-12%). Plasma apo B decreased to the greatest extent with gemfibrozil (-86%) followed by ciprofibrate (-47%), fenofibrate (-40%), clofibrate (-24%) and bezafibrate (-20%). Only gemfibrozil increased plasma apo E levels which are characteristically low in this rat model. Gemfibrozil, fenofibrate and ciprofibrate increased apo A-I concentrations. It is concluded that plasma lipid regulators which elevate HDL in this model might do so by altering the metabolism and hence plasma concentration of apoAI (fenofibrate, ciprofibrate) or both apo E and A-I (gemfibrozil). It is hypothesized that drugs which alter the metabolism of both HDL peptides result in the greatest HDL-C elevation in the rat.
Krause
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D000818:Animals; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000097:blood*; D001057:Apolipoproteins E / Q000097:blood*; D001629:Bezafibrate / Q000494:pharmacology; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D008076:Cholesterol, HDL / Q000097:blood; D002994:Clofibrate / Q000494:pharmacology; D002995:Clofibric Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D011345:Fenofibrate / Q000494:pharmacology; D058607:Fibric Acids; D015248:Gemfibrozil; D008297:Male; D010421:Pentanoic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014631:Valerates / Q000494:pharmacology*
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D058607:Fibric Acids; D010421:Pentanoic Acids; D014631:Valerates; D002995:Clofibric Acid; C019304:ciprofibrate; D002994:Clofibrate; D015248:Gemfibrozil; D011345:Fenofibrate; D001629:Bezafibrate