Effect of simvastatin on receptor mediated metabolism of low density lipoprotein in guinea pigs

YM‐53601, a novel squalene synthase inhibitor, reduces plasma cholesterol and triglyceride levels in several animal species

“…The effects of YM‐53601 were also examined in guinea‐pigs with a high nonHDL‐C to HDL‐C ratio. This is the only rodent model which responds to administration of HMG‐CoA reductase inhibitors ( Matsunaga et al ., 1991 ) and therefore suitable for comparison between YM‐53601 and pravastatin. In these animals YM‐53601 lowered plasma cholesterol levels much more effectively than pravastatin.…”

Guinea Pigs as Models to Study the Hypocholesterolemic Effects of Drugs

“…The effects of these statins, however, vary according to their physiochemical and pharmacokinetic characteristics including hydrophilicity, tissue specificity, and effectiveness (68). The mechanisms by which the HMG-CoA reductase inhibitors: atorvastatin (15)(16)(17)48), simvastatin (16,17,51,53), pravastatin (51,54), and lovastatin (6,7,48) lower cholesterol levels have been analyzed in guinea pigs.…”

“…Simvastatin: Simvastatin is a lipophilic drug, which crosses membrane layers via passive diffusion and, therefore, influences cholesterol synthesis in extrahepatic tissues as well as in the liver (42)(43)(44). At 10 mg/kg/day, simvastatin reduced plasma TC by 16%, LDL-C by 36% and TG by 13% and increased HDL-C by 29% in guinea pigs (53). In addition, Matsunaga et al (53) measured LDL turnover using intravenous injection of [ 131 I]LDL and [ 125 I]galactose to quantify the LDL receptor pathway.…”

“…At 10 mg/kg/day, simvastatin reduced plasma TC by 16%, LDL-C by 36% and TG by 13% and increased HDL-C by 29% in guinea pigs (53). In addition, Matsunaga et al (53) measured LDL turnover using intravenous injection of [ 131 I]LDL and [ 125 I]galactose to quantify the LDL receptor pathway. Simvastatin significantly increased the fractional catabolic rate (FCR) of the LDL receptor dependent pathway, whereas it had no effect on the LDL receptor-independent pathway.…”

“…The US National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III emphasizes that patients with CHD, or who have a risk of CHD and LDL cholesterol (LDL-C) levels >130 mg/dL, should receive drug therapy with a goal of reducing LDL-C to <100 mg/dL (23). To date, guinea pigs have been used to analyze the effects of numerous drug treatments, including 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (6,7,(15)(16)(17)48,51,53,54,77), Acyl-CoA:Cholesterol Acyltransferase (ACAT) inhibitors (40,46), cholestyramine (27,33,80,87), fibric acids (47,82), probucol (35), and apical sodium co-dependent bile acid transporter (ASBT) inhibitors (83,84). The growing incidence of dyslipidemia in Western societies reinforces the need for an appropriate animal model for the evaluation of cholesterol lowering drugs.…”