EFFECT OF FOOD ON THE RELATIVE BIOAVAILABILITY OF A HYPOLIPIDEMIC AGENT (CGP-43371) IN HEALTHY-SUBJECTS

The relative bioavailability of a capsule formulation and the effects of food on the pharmacokinetics of a hypolipidemic agent (CGP 43371) in 12 healthy subjects were examined. Each subject randomly received a single dose of 800 mg of CGP 43371, either as a dispersion formulation under fasting conditions or as a capsule formulation under fasting and fed conditions in a three-way crossover design with a washout period of 2 weeks between each treatment. Serial blood samples were collected at frequent intervals up to 96 h after each treatment. The concentrations of CGP 43371 in plasma were determined by a normal-phase HPLC method. Similar mean pharmacokinetic data (peak plasma drug concentration, 0.16 versus 0.18 mu g/mL; area under the plasma drug concentration-time curve from time zero to infinity, 4.56 versus 4.22 mu g.h/mL; time to the peak plasma drug concentration, 10.3 versus 10.2 h; lag time, 3.7 versus 3.8 h; and terminal elimination half-life, 17.8 versus 15.0 h) for the dispersion and capsule formulations under fasting conditions indicated that both formulations were bioequivalent with respect to the rate and extent of absorption. In contrast, the mean peak plasma drug concentration (2.01 mu g/mL) and area under the curve from time zero to infinity (57.35 mu g.h/mL) for the capsule formulation with food were enhanced similar to 11- and 14-fold, respectively, when compared with that without food. The corresponding mean lag time (2.1 h) was decreased similar to 50%. These differences in pharmacokinetic parameters were statistically significant, on the basis of an analysis of variance. On the other hand, the mean time to the peak plasma drug concentration (12.5 h) and terminal elimination half-life(17.7 h) were not significantly different. The results of this study demonstrated that the ingestion of a standard meal significantly increased the rate and extent of absorption but did not affect the elimination of CGP 43371.