Effect of food on the bioavailability of atorvastatin, an HMG-CoA reductase inhibitor.
To determine whether atorvastatin, a new HMG-CoA reductase inhibitor, could be administered with food in Phase II and III clinical trials, a nonblind, randomized, two-way crossover study was conducted to assess the effect of food on rate and extent of atorvastatin absorption. Sixteen healthy volunteers received single 80-mg atorvastatin capsule doses on two occasions one week apart: once after an 8-hour overnight fast and once with a medium-fat breakfast. The single 80-mg atorvastatin capsule doses were well-tolerated. Mean maximum plasma atorvastatin equivalent concentration (Cmax) and area under the concentration-time curve (AUC) values with food were 47.9% and 12.7% lower, respectively, than without food. Mean time of maximum observed concentration (tmax) and elimination half-life (t1/2) values were 5.9 and 32.0 hours, respectively, with food and 2.6 and 35.7 hours, respectively, without food. A medium-fat breakfast decreased the rate of atorvastatin absorption significantly, but had little impact on extent of drug absorption. Changes in rate of atorvastatin absorption are not expected to have a clinically significant effect, as subsequent multiple-dose clinical studies have shown that dose but not plasma atorvastatin concentration profiles correlates with lipid-lowering effects.
Radulovic
L L
LL
Department of Pharmacokinetics/Drug Metabolism, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Michigan 48105, USA.
Cilla
D D
DD
Posvar
E L
EL
Sedman
A J
AJ
Whitfield
L R
LR
D000284:Administration, Oral; D000328:Adult; D000069059:Atorvastatin; D001682:Biological Availability; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics*; D005215:Fasting / Q000097:blood; D005260:Female; D018565:Food-Drug Interactions; D006538:Heptanoic Acids / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000493:pharmacokinetics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000097:blood / Q000493:pharmacokinetics*
D004041:Dietary Fats; D004791:Enzyme Inhibitors; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D006903:Hydroxymethylglutaryl CoA Reductases