HMG-CoA reductase activity in human liver microsomes: comparative inhibition by statins.
The aim of this study was to compare a number of vastatins, HMG-CoA reductase inhibitors, in human liver microsomes. HMG-CoA reductase activity was four times lower than the activity in untreated rat liver microsomes. Vastatins could be classified in this in vitro assay in three classes both in human and rat microsomes: the first one including cerivastatin with an IC50 of 6 nM, the second one with atorvastatin and fluvastatin (IC50) between 40 and 100 nM) and the third one containing pravastatin, simvastatin and lovastatin (IC50 between 100 and 300 nM).
Dansette
P M
PM
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, URA 400 CNRS, Université Rene Descartes, Paris, France. dansette@biomedicale.univ-paris5.fr
Jaoen
M
M
Pons
C
C
D000818:Animals; D000069059:Atorvastatin; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D017035:Pravastatin / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology; D013045:Species Specificity
D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D011725:Pyridines; D011758:Pyrroles; D000077340:Fluvastatin; D008148:Lovastatin; D000069059:Atorvastatin; D019821:Simvastatin; C086276:cerivastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D017035:Pravastatin