A new fenofibrate formulation: results of six single-dose, clinical studies of bioavailability under fed and fasting conditions

Abstract

Background: The main drawback of the lipid-lowering agent fenofibrate is low bioavailability when taken orally on an empty stomach. Even the newest marketed formulations, micronized fenofibrate (MF) 200-mg capsules and microcoated fenofibrate (MCF) 160-mg tablets, require administration with meals to increase bioavailability. Insoluble Drug Delivery-Microparticle (IDD-P) fenofibrate 160-mg tablets are a new formulation developed to provide bioavailability independent of food.

Objective: The aims of this group of studies were to determine the effects of food on the bioavailability of IDD-P fenofibrate and MCF and to compare the bioavailabilities of IDD-P fenofibrate, MF, and MCF under fasting and fed conditions.

Methods: Six single-dose pharmacokinetic studies were conducted in healthy adult volunteers. The primary end points were the extrapolated area under the curve (AUC) from time 0 to infinity (AUC(0-infinity)), the experimental AUC from time 0 to time t, and the maximum plasma concentration of the active fenofibrate metabolite, fenofibric acid. The bioavailabilities of tested treatments were compared using the 90% CIs of ratios of least squares means (RLSMs) of logarithmically transformed AUC(0-infinity) values; 90% CIs within 80% to 125% were considered to indicate equivalent bioavailability (ie, extent of absorption).

Results: One hundred thirteen subjects (87 men, 26 women) received > or =1 study treatment and were evaluable for tolerability, and 99 of them (77 men, 22 women) were evaluable for bioavailability. The RLSMs of IDD-P fenofibrate extent of absorption (AUC(0-infinity)) under fed versus fasting conditions were 104.99%, 118.76%, and 113.56% (high-fat fed) and 111.06% and 110.64% (low-fat fed) in 5 separate comparisons. The corresponding 90% CIs were 95.38% to 115.58%, 113.38% to 124.40%, 107.54% to 119.93%, 106.06% to 116.32%, and 104.75% to 116.86%. All of these CIs were within the 80% to 125% range, suggesting equivalent bioavailability of IDD-P fenofibrate independent of food. The RLSM for MCF under high-fat fed versus fasting conditions was 151.19% (90% CI, 123.59%-184.94%).

Conclusions: In healthy adult volunteers, IDD-P fenofibrate had an equivalent extent of absorption under fed or fasting conditions, suggesting that dosage regimens could include administration of the product without food. Administering drug independently of food may provide greater convenience and simplicity for patients and prescribers.