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 (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, 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.