Pharmacokinetic interaction between propranolol and the HMG-CoA reductase inhibitors pravastatin and lovastatin.
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.
Pan
H Y
HY
Bristol-Myers Squibb Pharmaceutical Research Institute, New Brunswick, NJ.
Triscari
J
J
DeVault
A R
AR
Smith
S A
SA
Wang-Iverson
D
D
Swanson
B N
BN
Willard
D A
DA
D000328:Adult; D000924:Anticholesteremic Agents / Q000493:pharmacokinetics*; D001681:Biological Assay; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics; D008401:Gas Chromatography-Mass Spectrometry; D006538:Heptanoic Acids / Q000493:pharmacokinetics*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin / Q000493:pharmacokinetics*; D008297:Male; D009281:Naphthalenes / Q000493:pharmacokinetics*; D017035:Pravastatin; D011433:Propranolol / Q000494:pharmacology*; D011897:Random Allocation; D012016:Reference Values
D000924:Anticholesteremic Agents; D004791:Enzyme Inhibitors; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009281:Naphthalenes; D008148:Lovastatin; D011433:Propranolol; D017035:Pravastatin