The effects of food on the bioavailability of fenofibrate administered orally in healthy volunteers via sustained-release capsule

초록

Objective: To examine the effects of food on plasma concentration and bioavailability of fenofibrate administered as a sustained-release capsule. Methods: 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 (250mg 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. Results: 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. Conclusion: 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.

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