Effects of simvastatin, a lipoprotein-lowering drug, on the hepatic enzymes involved in drug metabolism in the Wistar rat.
1. Simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl glutaryl CoA reductase, lowers the plasma cholesterol level and has been approved for treatment of hyperlipoproteinaemia. 2. Simvastatin has been studied for its effects on hepatic microsomal drug metabolism in rat. No induction of 7-ethoxyresorufin-O-deethylase (EROD), ethoxycoumarin-O-deethylase (ECOD) and of UDP-glucuronosyltransferases were found, in vitro, after administration of 0.5, 1.5 and 10 mg/kg per day for 22 days. 3. Epoxide hydrolases (microsomal and cytosolic) were also unchanged after treatment with simvastatin. 4. No increase of the palmitoyl CoA oxidase activity or of mitochondrial glycerol phosphate dehydrogenase activity occurred. 5. Fatty acid distribution in rat liver microsomal phosphatidylcholines showed a significant decrease of C16:1 and a significant increase of C20:4 acids.
Mercenne
F
F
Formation de Biochimie Pharmacologique, UFR de Pharmacie et de Médecine, Dijon, France.
Goudonnet
H
H
Mounie
J
J
Escousse
A
A
Truchot
R C
RC
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D004851:Epoxide Hydrolases / Q000096:biosynthesis; D005227:Fatty Acids / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000096:biosynthesis; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000096:biosynthesis; D010713:Phosphatidylcholines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D019821:Simvastatin; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
D005227:Fatty Acids; D000960:Hypolipidemic Agents; D010713:Phosphatidylcholines; D008148:Lovastatin; D019821:Simvastatin; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D005993:Glycerolphosphate Dehydrogenase; C028427:palmitoyl CoA oxidase; D004851:Epoxide Hydrolases