EFFECT OF FOOD ON THE BIOAVAILABILITY OF ATORVASTATIN, AN HMG-COA REDUCTASE INHIBITOR

To determine whether atorvastatin, a nerv 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 asses s the effect of food on rate and extent of atorvastatin absorption. Si xteen healthy volunteers received single 80-mg atorvastatin capsule do ses on two occasions one week apart: once after an 8-hour overnight fa st and once with a medium-fat breakfast. The single 80-mg atorvastatin capsule doses were well-tolerated. Mean maximum plasma atorvastatin e quivalent concentration (C-max) 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 (t(max )) and elimination half-life (t1/2) values were 5.9 and 32.0 hours, re spectively, with food and 2.6 and 35.7 hours, respectively, without fo od. A medium-fat breakfast decreased the rate of atorvastatin absorpti on 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 st udies have shown that dose but not plasma atorvastatin concentration p rofiles correlates with lipid-lowering effects.