Bruce D. Roth Pages 139 - 154 ( 16 )
The utility of inhibitors of the enzyme HMG-CoA reductase for lowering plasma total and low-density lipoprotein cholesterol is now indisputable. Considerable research is now ongoing to determine whether these inhibitors will possess anti-atherosclerotic activity, either indirectly due to their lipid-regulating properties or due to a direct effect on atherosclerotic and/or restenotic lesion formation. Much of this research is based on the premise that the ability of these inhibitors to block lesion formation and/or induce lesion regression will be dependent on their ability to penetrate into tissues, which may be dependent on their physicochemical properties. Despite the results of pre-clinical animal model research suggesting that the differing abilities of lipophilic and hydrophilic inhibitors to penetrate into tissues results in discernable differences in pharmacology, these differences seem to disappear clinically. This review will discuss ongoing research to differentiate inhibitors based on their ability to directly effect arterial lesions and attempt to explain these results in terms of the physicochemical properties of inhibitors.