HYDROPHILICITY LIPOPHILICITY - RELEVANCE FOR THE PHARMACOLOGY AND CLINICAL EFFECTS OF HMG-COA REDUCTASE INHIBITORS/

The recent development of specific competitive inhibitors of the hydro xymethylglutaryl coenzyme A (HMG-CoA) reductase such as lovastatin, si mvastatin, pravastatin and fluvastatin has provided an important new a nd effective approach to the treatment of hyperlipidaemia and atherosc lerosis. These agents are designed to be hepatoselective because the p rimary site of cholesterol synthesis is the liver and peripheral inhib ition of cholesterol synthesis would be more likely to cause adverse d rug effects. In this review, Bettina Hamelin and Jacques Turgeon discu ss how specific physico-chemical and pharmacological properties (first -pass effect or carrier-mediated uptake) confer hepatoselectivity to e ither lipophilic or hydrophilic HMG-CoA reductase inhibitors.