Irbesartan does not affect the pharmacokinetics of simvastatin in healthy subjects.
This open-label, single-dose, crossover study was conducted to assess the effect of irbesartan on the pharmacokinetics of total simvastatin acid in 14 healthy subjects. Subjects were randomized to receive one simvastatin 40 mg tablet or one simvastatin 40 mg tablet + one irbesartan 300 mg tablet. Subjects were crossed over to the other treatment after a 7- to 10-day washout period. Serum samples were collected at specified times before and over a 24-hour period after dosing. Safety was assessed by monitoring vital signs, laboratory tests, and adverse events. Irbesartan did not exhibit a clinically significant effect on the peak serum concentration and area under the concentration versus time curve to infinity (AUC0-infinity) of total simvastatin acid. The mean AUC0-infinity of total simvastatin acid was 74.55 ng x h/mL when simvastatin was given alone and 67.55 ng x h/mL when simvastatin and irbesartan were given concomitantly. The time to peak serum concentration for both treatments was 3 hours. No serious adverse events occurred during the study, and both agents were well tolerated. In summary, irbesartan had no significant effect on the single-dose pharmacokinetics of total simvastatin acid.
Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey, USA.
M R
MR
Marino
N N
NN
Vachharajani
O W
OW
Hadjilambris
D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases; D001713:Biphenyl Compounds / Q000494:pharmacology*; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004347:Drug Interactions; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D000077405:Irbesartan; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D019821:Simvastatin / Q000009:adverse effects / Q000493:pharmacokinetics*; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors; D013777:Tetrazoles / Q000494:pharmacology*
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D065607:Cytochrome P-450 Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013777:Tetrazoles; D019821:Simvastatin; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D039181:Steroid 16-alpha-Hydroxylase; D000077405:Irbesartan