Hypocholesterolemic effects of 3-hydroxy-3-methylglutaryl coenzyme a (HMG-CoA) reductase inhibitors in the guinea - Atorvastatin versus simvastatin

Male Hartley guinea pigs were fed a hypercholesterolemic diet rich in lauri c and myristic acids with 0, 10, or 20 mg/kg of simvastatin or atorvastatin for 21 days. Atorvastatin and simvastatin resulted in a lowering of plasma law density lipoprotein (LDL) cholesterol in a dose-dependent manner by an average of 48 and 61% with 10 and 20 mg/kg, respectively. Both statins wer e equally effective in lowering plasma LDL cholesterol and apolipoprotein B (apo B) levels. Atorvastatin and simvastatin treatments yielded LDL partic les that differed in composition from the control. Due to the relevance of LDL oxidation and cholesteryl ester transfer in plasma to the progression o f atherosclerosis, these parameters were analyzed after statin treatment. A torvastatin and simvastatin treatment decreased the susceptibility of LDL p articles to oxidation by 95% as determined by the formation of thiobarbitur ic acid reactive substances. An 80% decrease in the transfer of cholesteryl ester between high density lipoprotein (HDL) and the apo-B containing lipo proteins was observed after simvastatin and atorvastatin treatment. In addi tion, statin effects on plasma LDL transport were studied. Simvastatin- and atorvastatin-treated guinea pigs exhibited 125 and 175% faster LDL fractio nal catabolic rates, respectively, compared with control animals. No change in LDL apo-B flux was induced by either treatment; however, LDL apo-B pool size was reduced after statin treatment. Hepatic microsomal free cholester ol was lower in the atorvastatin and simvastatin groups. However, only ator vastatin treatment resulted in an 80% decrease of acyl-CoA:cholesterol acyl transferase activity (P < 0.001). In summary, atorvastatin and simvastatin had similar LDL cholesterol lowering properties, but these drugs modified L DL transport and hepatic cholesterol metabolism differently. (C) 1999 Elsev ier Science Inc.