Comparative Pharmacokinetics and Pharmacodynamics of Pravastatin and Lovastatin

The oral bioavailability of two HMG‐CoA reductase inhibitors, pravastatin and lovastatin, was investigated in this randomized, two‐way crossover study. Twenty healthy men were randomly assigned to treatment with a 40‐mg dose of pravastatin or lovastatin once daily for 1 week; steady state kinetics were assessed after the last dose. After 1 week of washout, each subject received the alternate treatment. Serum specimens were assayed by gas chromatography/mass spectrometry (GC/MS) for intact pravastatin or lovastatin acid and by bioassay for active inhibitor concentration and, after hydrolysis of lactones, for total inhibitor concentration. The systemic bioavailabilities of total (active plus potentially active) inhibitors for the two drugs were different, with the mean AUC value for lovastatin being 50% higher than that of pravastatin (mean ± SEM AUC 0−24 values of 285 ± 25 and 189 ± 13 ng‐equiv × hr/mL, respectively, P < .0001). Pravastatin, which is administered as the monosodium salt, is present in the systemic circulation as the open acid; lovastatin, which is administered as the lactone, is present as both open‐acid active metabolites (62%) and closed‐ring lactone metabolites (38%), which are potentially active. Based on mean AUC values, pravastatin accounted for 75% of the active inhibitors from a pravastatin dose. Lovastatin acid accounted for just 25% of the active inhibitors from a lovastatin dose, with the remainder due to other active metabolites. Significant decreases from baseline in total and low‐density lipoprotein (LDL) cholesterol were observed during the first treatment leg for both pravastatin and lovastatin. Pravastatin treatment resulted in 21% and 26% decreases in total and LDL‐cholesterol, respectively (P < .001); lovastatin reduced these parameters by 18% and 22%, respectively (P < .003). These results indicate that, although pravastatin and lovastatin have very similar chemical structures and effects on serum lipids, they differ sharply in pharmacokinetic properties.