Species differences in the inhibiting effect of fluvastatin, a new inhibitor of HMG-CoA reductase, on cholesterol biosynthesis.
Cholesterol synthesis both ex vivo and in vivo in liver and ileum of hamsters was significantly inhibited by fluvastatin. This ex vivo inhibition was considerably lower in fluvastatin-treated hamsters than in fluvastatin-treated rats. In hamsters and rats, fluvastatin was more potent than pravastatin on inhibitory activities of sterol synthesis in liver, but not in the hamster ex vivo. This may indicate that, in part, the hydrophobicity of the fluvastatin molecule confers the selectivity and metabolism in the liver of hamsters and rats to originate from the species differences.
Yamamoto
A
A
Department of Pharmacology, Hokkaido Institute of Pharmaceutical Sciences, Otaru, Japan.
Itoh
S
S
Hoshi
K
K
Ichihara
K
K
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002784:Cholesterol / Q000096:biosynthesis*; D006224:Cricetinae; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D017035:Pravastatin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D000077340:Fluvastatin; D002784:Cholesterol; D017035:Pravastatin