Pravastatin, lovastatin and simvastatin are HMG-CoA reductase inhibitors with very similar structures. However, minor substitutions in the decalin ring have resulted in major differences in physiocochemical, pharmacological, and pharmacokinetic properties. Both in vitro and in vivo studies have demonstrated that lovastatin and simvastatin are non-selective lipophilic inhibitors, while pravastatin is a selective hydrophilic inhibitor. An extensive clinical pharmacology program has been conducted for pravastatin. Radiolabelled studies demonstrated oral absorption and bioavailability values of 34% and 17%, respectively. The parent drug is cleared equally by renal and non-renal routes. Peak blood level after oral administration is reached at approximately 1 h and the mean plasma elimination half-life is 1.8 h. Binding of total radioactivity to plasma proteins averages 45%. Non-radiolabelled studies showed that mean areas under the plasma concentration-time curves (AUC) and maximum plasma concentrations (Cmax) are proportional to the doses administered, whereas times to reach Cmax (Tmax) and plasma elimination half-life values are independent of dose. Measurement of trough plasma concentrations of pravastatin at steady state showed no evidence of drug accumulation. Pharmacodynamic studies demonstrated an average LDL-C decrease of 30-35% at a daily dose of 40 mg. HDL-C increases are between 10% and 25% and triglyceride decreases, between 10% and 25%. These results indicate that pravastatin is very effective in lowering LDL-C. With its consistent decrease in triglycerides and increase in HDL-C, pravastatin offers a well-balanced lipid-modulating response.