Micronized Fenofibrate: A New Fibric Acid Hypolipidemic Agent

Guay, David R.P.

doi:10.1345/aph.18432

Cited by 68 publications

(64 citation statements)

References 116 publications

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“…The half-life of fenofibrate has been reported to be 20 h in individuals with normal renal functions, and the level of fenofibrate required to achieve IC 50 for MCL is within the therapeutic range that is used to treat hyperlipidemia. [43][44][45][46] In light of the excellent safety, tolerability and affordability of fenofibrate, there is merit in investigating the possibility of extending the clinical use of fenofibrate, either as a sole agent or in combination with conventional chemotherapy, in the treatment of MCL.…”

Section: Minomentioning

confidence: 99%

Fenofibrate induces effective apoptosis in mantle cell lymphoma by inhibiting the TNFα/NF-κB signaling axis

2010

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Mantle cell lymphoma (MCL) is a type of aggressive B-cell non-Hodgkin's lymphoma characterized by frequent resistance to conventional chemotherapy. In this study we provided evidence that fenofibrate, which is widely known as an agonist for peroxisome proliferator-activated receptor-a (PPARa), can induce effective apoptosis in treating MCL cells. Addition of fenofibrate to MCL cell lines significantly decreased the number of viable cells by 50% at approximately 20 lM at 72 h. This decrease in cell growth was due to apoptosis, as evidenced by the cleavage of caspase 3 and poly(ADP-ribose) polymerase. The fenofibrate-mediated effects were not significantly affected by GW6471, a specific PPARa antagonist. Using an apoptosis pathway-specific oligonucleotide array, we found that fenofibrate significantly downregulated several pro-survival genes, including tumor necrosis factor-a (TNFa). Importantly, addition of recombinant TNF-a conferred partial protection against fenofibrate-induced apoptosis. Fenofibrate also decreased the nuclear translocation of nuclear factor (NF)-jB-p65 and significantly inhibited the DNA binding of NF-jB in a dose-dependent manner. To conclude, fenofibrate shows efficacy against MCL, and the mechanism can be attributed to its inhibitory effects on the TNF-a/NF-jB signaling axis. In view of the documented safety of fenofibrate in humans, it may provide a valuable therapeutic option for MCL patients.

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Section: Minomentioning

confidence: 99%

Fenofibrate induces effective apoptosis in mantle cell lymphoma by inhibiting the TNFα/NF-κB signaling axis

2010

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“…This metabolite is responsible for the primary pharmacodynamic effects of reductions in total plasma cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and very low-density lipoprotein (VLDL) concentrations and increases in high-density lipoprotein cholesterol (HDL-C) and apolipoproteins (Apo) AI and AII concentrations (33).…”

Section: Pharmacodynamicsmentioning

confidence: 99%

“…A comprehensive review of the product was published in late 1999 (33). The current paper will update this review, covering the pharmacology, pharmacokinetics, clinical efficacy, tolerability, drug interactions, pharmacoeconomics, and dosing recommendations of fenofibrate.…”

Section: Introductionmentioning

confidence: 99%

Update on Fenofibrate

Guay

2002

Cardiovascular Drug Reviews

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Fenofibrate is a fibric acid derivative that has been marketed since the mid-1970's (1998 in the United States). Its active metabolite, fenofibric acid, is responsible for the primary pharmacodynamic effects of the drug: reductions in total plasma cholesterol, lowdensity lipoprotein cholesterol, triglycerides, and very low-density lipoprotein concentrations and increases in high-density lipoprotein cholesterol and apolipoproteins AI and AII concentrations. These effects are mediated by activation of peroxisome proliferator-activated receptor-á (PPAR á ). The drug has broad spectrum utility, with documented efficacy in Fredrickson types IIa, IIb, III, IV, and V hyperlipidemias. Fenofibrate is well tolerated, with digestive and musculoskeletal side effects similar to those of other fibrates. Results of the initial cardiovascular morbidity/mortality outcomes study with fenofibrate (known as DAIS [Diabetes Atherosclerosis Intervention Study]) were encouraging vis-à-vis slowing of atherosclerotic progression in the coronary vasculature of type II diabetics. The results of other ongoing outcome trials are eagerly awaited. These results will help to establish the overall place of fenofibrate in the hypolipidemic armamentarium.

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“…1,2 It is a very lipophilic entity (logP =5. 24) 3 that is practically insoluble in aqueous gastrointestinal fluids (,100 μg/mL); 4 therefore, it exhibits very poor absorption 5 and bioavailability after oral administration.…”

Section: Introductionmentioning

confidence: 99%

“…24) 3 that is practically insoluble in aqueous gastrointestinal fluids (,100 μg/mL); 4 therefore, it exhibits very poor absorption 5 and bioavailability after oral administration. 1 Thus, an enhancement in bioavailability is dependent upon an improvement in aqueous solubility.…”

Section: Introductionmentioning

confidence: 99%

Novel electrosprayed nanospherules for enhanced aqueous solubility and oral bioavailability of poorly water-soluble fenofibrate

Yousaf

Mustapha

Kim

et al. 2016

IJN

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Purpose The purpose of the present research was to develop a novel electrosprayed nanospherule providing the most optimized aqueous solubility and oral bioavailability for poorly water-soluble fenofibrate. Methods Numerous fenofibrate-loaded electrosprayed nanospherules were prepared with polyvinylpyrrolidone (PVP) and Labrafil ® M 2125 as carriers using the electrospray technique, and the effect of the carriers on drug solubility and solvation was assessed. The solid state characterization of an optimized formulation was conducted by scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopic analyses. Oral bioavailability in rats was also evaluated for the formulation of an optimized nanospherule in comparison with free drug and a conventional fenofibrate-loaded solid dispersion. Results All of the electrosprayed nanospherule formulations had remarkably enhanced aqueous solubility and dissolution compared with free drug. Moreover, Labrafil M 2125, a surfactant, had a positive influence on the solubility and dissolution of the drug in the electrosprayed nanospherule. Increases were observed as the PVP/drug ratio increased to 4:1, but higher ratios gave no significant increases. In particular, an electrosprayed nanospherule composed of fenofibrate, PVP, and Labrafil M 2125 at the weight ratio of 1:4:0.5 resulted in a particle size of <200 nm with the drug present in the amorphous state. It demonstrated the highest solubility (32.51±2.41 μg/mL), an excellent dissolution (~85% in 10 minutes), and an oral bioavailability ~2.5-fold better than that of the free drug. It showed similar oral bioavailability compared to the conventional solid dispersion. Conclusion Electrosprayed nanospherules, which provide improved solubility and bioavailability, are promising drug delivery tools for oral administration of poorly water-soluble fenofibrate.

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Micronized Fenofibrate: A New Fibric Acid Hypolipidemic Agent

Cited by 68 publications

References 116 publications

Fenofibrate induces effective apoptosis in mantle cell lymphoma by inhibiting the TNFα/NF-κB signaling axis

Fenofibrate induces effective apoptosis in mantle cell lymphoma by inhibiting the TNFα/NF-κB signaling axis

Update on Fenofibrate

Novel electrosprayed nanospherules for enhanced aqueous solubility and oral bioavailability of poorly water-soluble fenofibrate

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