Summary
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′α-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.
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Ohtawa, M., Uchiyama, N. Sex difference in metabolism of simvastatin by rat hepatic microsomes. European Journal of Drug Metabolism and Pharmacokinetics 17, 175–181 (1992). https://doi.org/10.1007/BF03190142
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DOI: https://doi.org/10.1007/BF03190142