Comparative Pharmacokinetics and Pharmacodynamics of Pravastatin and Lovastatin

Abstract

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 AUC0-24 values of 285 +/- 25 and 189 +/- 13 ng-equiv x hr/mL, respectively, P less than .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.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of Monocyte Chemotactic Protein-1 Synthesis by Statins

“…For this study we used lovastatin, as a prototype of a lipophilic inhibitor of HMG-CoA reductase activity, and pravastatin, which, because of their different chemical structures, exhibit in vivo diverse pharmacological properties (Bhatnagar, 1998;Pan et al, 1990;Rosenson et al, 1999). The effect of these statins on leukocyte migration and chemokine production was investigated by applying the mouse air-pouch model of local inflammation (Romano et al, 1997).…”

Effects of bile salts on the lovastatin pharmacokinetics following oral administration to rats

“…Lovastatin is rapidly absorbed following administration, reaching the steady-state peak plasma concentration (T max ) within 4 h in humans (Pan et al, 1990). Due to the short elimination half-life of 1.1-1.7 h, lovastatin is best administered in the evening, when the rate of endogenous cholesterol synthesis is highest (Schachter, 2004;Lacy et al, 2009).…”

Steady state serum concentrations of pravastatin and digoxin when given in combination.

“…Although there were small (23% and 26%) increases in the mean AUC and Cmax values of pravastatin during co-administration of digoxin, the values of these parameters were within the ranges reported following single or multiple therapeutic doses of pravastatin [2][3][4]9] [10].…”