Pravastatin sodium (Pravastatin, CS-514, SQ-31000, Mevalotin@) (FIG. 1) is a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, a key enzyme of cholesterol biosynthesis.In the present study, tissue selectivity of pravastatin in inhibition of cholesterol synthesis was investigated in vitro and in vivo, and its effect was compared with other HMG-CoA reductase inhibitors, such as lovastatin (MB-530B, Mevinolin, Mevacor@), simvastatin (MK-733, Synvinolin, Zocora) and ML-236B (Compactin, Mevastatin) (FIG. 1). Inhibition of cholesterol synthesis in vivo was measured by incorporation of radioactivity into sterol fraction 1 hr after intraperitoneal injection of [ I4C]acetate to mice which were orally administered these drugs 2 hr before the acetate injection. When pravastatin was administered to mice at the dose of 20 mglkg, cholesterol synthesis was inhibited about 90% in the liver and ileum, but the inhibition was less than 10% in the kidney, spleen, adrenal, testis, prostate and brain. This tissue selectivity of pravastatin was also demonstrated even in varying doses (5-40 mg/kg) and time (75-180 min) after drug administration. Other HMG-CoA reductase inhibitors, such as lovastatin and simvastatin in both the lactone and open acid forms, and ML-236B did not show such a tissueselective inhibition as pravastatin (FIG. 2).These results were further confirmed by the inhibition of sterol synthesis in various cultured cells and rat lenses (TABLE 1). In freshly isolated rat hepatocytes, pravastatin and other HMG-CoA reductase inhibitors similarly inhibited the sterol synthesis. In the cells from nonhepatic tissues and rat lenses, lovastatin, simvastatin and ML-236B exerted a similar inhibitory activity as observed in rat hepatocytes. In contrast, the inhibitory activity of pravastatin was much less potent in these nonhepatic cells and rat lenses. This tissue selectivity of pravastatin could be explained by lesser cellular uptake of pravastatin into nonhepatic cells.Thus, pravastatin is shown to be a more distinct tissue-selective inhibitor of sterol synthesis in vitro and in vivo than other HMG-CoA reductase inhibitors. REFERENCE 1. TSUJITA, Y. er al. 1986. Biochim. Biophys. Acta 877: 50-60.