Abstract
In this communication we attempt to provide one possible explanation for the observed differences regarding kinetics and distribution between simvastatin and pravastatin. Rats treated with simvastatin or pravastatin exhibited a reduction in the incorporation of [2-14C]acetate into liver cholesterol and displayed lower plasma mevalonate levels as compared to control animals. Moreover, both the total and dephosphorylated 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (EC 1.1.1.34) activities, particularly 1 h after treatment, were greatly reduced in liver microsomes obtained from simvastatin-treated as compared to control rats. During the same time frame, these parameters were actually elevated with pravastatin treatment. It is known that HMG-CoA reductase synthesis and activity increase following their competitive inhibition. Our results suggest that pravastatin, at 1 h following treatment, was no longer bound to the enzyme; however, it had entered the liver because its inhibitory effect on cholesterol synthesis was manifest at early times after administration. These data provide a plausible rationale for the earlier observation that activity of simvastatin persists longer in plasma than does that of pravastatin.
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Abbreviations
- HMG-CoA:
-
3-Hydroxy-3-methylglutaryl-CoA
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Del Puppoo, M., Rauli, S. & Kienle, M.G. Inhibition of cholesterol synthesis and hepatic 3-hydroxy-3-methylglutaryl-CoA reductase in rats by simvastatin and pravastatin. Lipids 30, 1057–1061 (1995). https://doi.org/10.1007/BF02536292
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DOI: https://doi.org/10.1007/BF02536292