Lack of a clinically significant pharmacokinetic interaction between fenofibrate and pravastatin in healthy volunteers.
This study was conducted to evaluate the potential pharmacokinetic interaction between fenofibrate and pravastatin. A total of 23 healthy adult volunteers received single-dose 201 mg fenofibrate alone, 201 mg fenofibrate + 40 mg pravastatin, and 40 mg pravastatin alone in a three-period crossover experiment. Plasma samples were collected at predetermined times and were analyzed with validated methods for the quantitation of fenofibric acid, pravastatin, and 3 alpha-hydroxy-isopravastatin (3 alpha-iso-PV). Pharmacokinetic parameters of these three compounds were calculated using noncompartmental methods and compared by analyses of variance and bioavailability assessments. Concomitant administration of fenofibrate and pravastatin did not affect the pharmacokinetics of either fenofibric acid or pravastatin. However, the AUC0-infinity and Cmax of 3 alpha-iso-PV were increased by 26% and 29%, respectively. The moderate increase in the formation of this pravastatin metabolite should not raise any clinical concerns due to its much lower pharmacological potency compared to pravastatin and lack of toxicity.
Pan
W J
WJ
Department of Clinical Pharmacokinetics and Toxicokinetics, Abbott Laboratories, Abbott Park, Illinois 60064-6104, USA.
Gustavson
L E
LE
Achari
R
R
Rieser
M J
MJ
Ye
X
X
Gutterman
C
C
Wallin
B A
BA
D000328:Adult; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D004336:Drug Antagonism; D005260:Female; D011345:Fenofibrate / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000009:adverse effects / Q000493:pharmacokinetics*
D000924:Anticholesteremic Agents; D000960:Hypolipidemic Agents; C006012:fenofibric acid; D017035:Pravastatin; D011345:Fenofibrate