The Effects of Food on the Bioavailability of Fenofibrate Administered Orally in Healthy Volunteers via Sustained-Release Capsule

Abstract

To examine the effects of food on plasma concentration and bioavailability of fenofibrate administered as a sustained-release capsule. Twenty-four healthy Korean volunteers were enrolled in a randomised, open-label, balanced, three-treatment, three-period, three-sequence, single oral dose, crossover pharmacokinetic study. A single dose of fenofibrate (250 mg sustained-release capsule) was administered on three occasions -- after overnight fasting, after consumption of a standard breakfast and after a high-fat breakfast. Serial blood samples were collected for the next 72 hours. Plasma fenofibric acid concentrations were measured by high-performance liquid chromatography, and pharmacokinetic parameters were calculated. The pharmacokinetic parameters were significantly affected by food intake. The high-fat breakfast affected the rate of absorption of fenofibrate more than the standard breakfast and fasted conditions. Specifically, the area under the plasma concentration-time curve from time zero to infinity (AUC(infinity)) and peak plasma concentration (C(max)) increased 2.45-fold and 2.89-fold, respectively, between the fasted and standard-fed conditions (p < 0.01). In addition, the high-fat meal caused 3.34-fold and 3.82-fold increases compared with the fasted condition in AUC(infinity) and C(max), respectively. A one-compartment open model with lag time successfully described the plasma concentrations of fenofibric acid. In healthy volunteers, AUC(infinity) and C(max) of fenofibrate, when administered via sustained-release capsules immediately after the consumption of food, was increased significantly from the fasting conditions (p < 0.01). The greatest AUC(infinity) and C(max) occurred when the capsules were taken after a high-fat breakfast.