PT  - JOURNAL ARTICLE
AU  - M D Greenspan
AU  - J B Yudkovitz
AU  - A W Alberts
AU  - L S Argenbright
AU  - B H Arison
AU  - J L Smith
TI  - Metabolism of lovastatin by rat and human liver microsomes in vitro.
DP  - 1988 Sep 01
TA  - Drug Metabolism and Disposition
PG  - 678--682
VI  - 16
IP  - 5
4099  - http://dmd.aspetjournals.org/content/16/5/678.short
4100  - http://dmd.aspetjournals.org/content/16/5/678.full
SO  - Drug Metab Dispos1988 Sep 01; 16
AB  - The metabolism of lovastatin (Mevacor) was examined using isolated microsomes derived from the livers of normal and phenobarbital-treated rats and from human liver samples. Incubation of lovastatin with rat liver microsomes resulted in the formation of several polar metabolites of lovastatin. The metabolites were isolated by HPLC and identified by NMR and mass spectrometry. One fraction consisted of a 2:1 mixture of 6-hydroxy-lovastatin and the rearrangement product delta 4,5-3-hydroxy lovastatin. Addition of a trace of acid to this mixture resulted in the formation of a single aromatized product, the desacyl-delta 4a,6,8-dehydro analog of lovastatin. Another microsomal metabolite was determined to be the delta 4,8a,1-3-hydroxy-lovastatin derivative. The chromatographic pattern of metabolites produced from lovastatin by human liver microsomes was similar to that obtained with rat liver microsomes. Metabolism of lovastatin by rat liver microsomes was both time and concentration dependent; optimal microsomal metabolism occurred with 0.1 mM lovastatin, whereas higher lovastatin concentrations inhibited the reaction. The open acid form of lovastatin was poorly metabolized by both the rat and the human liver microsomes.