Micronized Fenofibrate in Dyslipidemia

Abstract

The prodrug fenofibrate, a synthetic phenoxy-isobutyric acid derivative, is rapidly hydrolyzed in vivo to form fenofibric acid, which alters plasma lipid levels by activating the peroxisome proliferator-activated receptor alpha. The micronized fenofibrate 200 mg capsule formulation, and the recently developed micronized fenofibrate 160 mg tablet formulation, are bioequivalent. Micronized fenofibrate 200 mg/day (capsules) increased high density lipoprotein cholesterol (HDL-C) levels significantly from baseline in up to 7098 patients with various dyslipidemias in noncomparative studies. Micronized fenofibrate 200 mg/day (capsules) produced significantly greater elevations in HDL-C levels than a variety of HMG-CoA reductase inhibitors in small, randomized, double-blind and nonblind studies in patients with dyslipidemia (n = 91 to 227). This formulation of fenofibrate and gemfibrozil produced similar increases in HDL-C levels in a randomized, double-blind study (n = 234). Micronized fenofibrate 160 mg once daily (tablet) increased HDL-C levels significantly from baseline by 10.6 to 14.5% in patients with type IIa or IIb dyslipidemia (n = 353) in two noncomparative studies. Additionally, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and LDL-C to HDL-C and TC to HDL-C ratios were lowered significantly from baseline. The tablet and capsule formulations of fenofibrate were both generally well tolerated in two noncomparative studies in 375 or 9884 patients. In double-blind, placebo-controlled trials in a total of 804 patients, the pooled incidences of individual adverse events were generally similar with fenofibrate and placebo.

Modulation of Urate Transport by Drugs

“…Fenofibrate is a lipid-lowering agent that is promptly hydrolyzed to its active metabolite fenofibric acid [ 131 ]. Fenofibrate is an inhibitor of BCRP, but this effect is unlikely to be clinically significant ( Table 3 ).…”

Development and validation of a rapid UHPLC-MS/MS method for the determination of fenofibric acid in human plasma: Application to a pharmacokinetic study of fenofibrate tablet in Chinese subjects

“…Fenofibrate is a prodrug that is hydrolyzed immediately after absorption by tissue and plasma esterases to its active major metabolite, FA. No unchanged fenofibrate is found in human plasma [8]. Therefore, FA was the detected drug in many pharmacokinetic studies of fenofibrate after oral administration [9][10][11].…”

Preparation and Characterization of Fenofibrate-Loaded PVP Electrospun Microfibrous Sheets

“…For BCS Class II drugs, solubility is the rate-limiting step in absorption. In order to overcome this problem, numerous fenofibrate formulations have been developed, and an excellent review [9] was also published about the available fenofibrate and fenofibric acid formulations Versatile types of formulations, e.g., micronized [10,11], microcoated [12,13], insoluble drug delivery microparticulate formulations [14], self-emulsifying drug delivery systems [15][16][17], nanoparticulate formulations [18][19][20][21], thin film freezing [22], incorporation in mesoporous silica [23][24][25][26][27][28], or carbon [29] have appeared in the last decade. In recent years, electrostatic spinning (electrospinning) has emerged as the most dynamically growing technique for the generation of artificial fibrous architectures [30,31].…”