Sex difference in metabolism of simvastatin by rat hepatic microsomes.
Metabolism of simvastatin (SV), a new cholesterol-lowering agent, by hepatic microsomes from male and female rats was investigated. After incubation of [14C]-SV with hepatic microsomes, radioactive metabolites were detected by HPLC. The main metabolite was 3' alpha-hydroxy-SV in male rats and the hydroxy open acid form of SV (SVA) in females. The 3"-hydroxy-SV and 3',3"-dihydroxy-SV which were observed in male rats were hardly detected in females. Specific activity for the metabolism of SV in male rats (3.97 nmol/mg protein/min) was about 9-times higher than that in females. Metabolic activity of hepatic microsomes in male rats was essentially unchanged with increase in age, whereas that in females decreased age-dependently and was very low or negligible after 7 weeks of age. Formation of 3"-hydroxy-SV and 3',3"-dihydroxy-SV in male rats was markedly increased with age, and that in females was negligible at all ages examined.
Ohtawa
M
M
Department of Drug Metabolism, Banyu Pharmaceutical Co Ltd, Tokyo, Japan.
Uchiyama
N
N
D000375:Aging / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000378:metabolism; D002250:Carbon Radioisotopes; D003577:Cytochrome P-450 Enzyme System; D005260:Female; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D019821:Simvastatin
D000924:Anticholesteremic Agents; D002250:Carbon Radioisotopes; D003577:Cytochrome P-450 Enzyme System; D008148:Lovastatin; D019821:Simvastatin