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


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.


CONCLUSIONS
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.
Yun
Hwi-Yeol
HY
College of Pharmacy, Chungnam National University, Daejeon, Korea.
Joo Lee
Eun
E
Youn Chung
Soo
S
Choi
Sun-Ok
SO
Kee Kim
Hyung
H
Kwon
Jun-Tack
JT
Kang
Wonku
W
Kwon
Kwang-Il
KI
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002214:Capsules; D003692:Delayed-Action Preparations; D004041:Dietary Fats / Q000494:pharmacology; D005215:Fasting / Q000378:metabolism; D005260:Female; D011345:Fenofibrate / Q000097:blood / Q000493:pharmacokinetics*; D018565:Food-Drug Interactions; D006801:Humans; D000960:Hypolipidemic Agents / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male
D002214:Capsules; D003692:Delayed-Action Preparations; D004041:Dietary Fats; D000960:Hypolipidemic Agents; D011345:Fenofibrate