Pharmacokinetic interaction between propranolol and the HMG‐CoA reductase inhibitors pravastatin and lovastatin.

Abstract

1. Single oral 20 mg doses of the HMG‐CoA reductase inhibitors pravastatin and lovastatin, with and without concomitant propranolol (40 mg twice daily), were administered to 16 healthy male subjects participating in a randomized, four‐way crossover study. 2. Serum concentrations of total and active inhibitors were measured by bioassay and concentrations of pravastatin, two pravastatin metabolites and lovastatin acid were measured by gas chromatography/mass spectrometry. 3. Coadministration of propranolol with pravastatin reduced the mean area under the serum concentration‐time curve (AUC) of total inhibitors by 23%, of active inhibitors by 20% and of pravastatin by 16%. 4. Coadministration of propranolol with lovastatin also resulted in decreases in the mean serum AUC of total inhibitors by 18%, of active inhibitors by 12% and of lovastatin acid by 13%. 5. These decreases in systemic drug concentrations may reflect enhanced drug first‐pass hepatic clearance in the presence of propranolol. 6. The clinical significance of these changes is likely to be small.