Efficacy and safety profile of fenofibrate-coated microgranules 130 mg, with and without food, in patients with hypertriglyceridemia and the metabolic syndrome: An 8-week, randomized, double-blind, placebo-controlled study

Davidson, Michael; Bays, Harold; Rhyne, James M.; Stein, Evan A.; Rotenberg, Keith S.; Doyle, Ralph T.

doi:10.1016/j.clinthera.2005.06.017

Cited by 11 publications

(6 citation statements)

References 24 publications

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“…There is evidence that this product is better absorbed with a high-fat meal; when administered with a high-fat meal, there was a 26% increase in fenofibric acid bioavailability and a 108% increase in maximum concentration compared with the fasting state [29]. Despite the pharmacokinetic implications of taking Antara ® with a high-fat meal, data from a clinical study showed comparable outcomes on serum triglycerides and cholesterol concentrations when Antara ® (130 mg) was taken once daily with or between meals [45]. Thus, although this study suggested differences in bioequivalence under the fasting and fed states, efficacy was less affected by administration with food and formed the basis for the indication to administer the drug without regard to meals.…”

Section: Resultsmentioning

confidence: 99%

A Review of Currently Available Fenofibrate and Fenofibric Acid Formulations

Ling

2013

Cardiol Res

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Fenofibrate is a third-generation fibric acid derivative indicated as a monotherapy to reduce elevated low-density lipoprotein cholesterol, total cholesterol, triglycerides, and apolipoprotein B; to increase high-density lipoprotein cholesterol in patients with primary hyperlipidemia or mixed dyslipidemia; and to reduce triglycerides in patients with severe hypertriglyceridemia. In this review, the key characteristics of available fenofibrate formulations are examined. A literature search was conducted, focusing on comparative studies examining bioavailability, food effects, absorption, and lipid efficacy. Fenofibrate is highly lipophilic, virtually insoluble in water, and poorly absorbed. Coadministration with meals was necessary to maximize bioavailability of early formulations. Micronized and nanoparticle formulations of fenofibrate with reduced particle sizes were developed, resulting in greater solubility, improved bioavailability, and in some cases, the ability to be given irrespective of food. A recently introduced hydrophilic choline salt of fenofibric acid also can be taken without regard to meals, is absorbed throughout the gastrointestinal tract, has the highest bioavailability among marketed formulations, and is approved for coadministration with a statin. Differences in bioavailability of fenofibrate formulations have resulted in low-dose (40 -67) mg and standard-dose (120 -200 mg) formulations. Different formulations are not equivalent on a milligram-to-milligram basis. In order to prevent medication errors, resulting in underdosing or overdosing with attendant consequences, it is important for healthcare providers to recognize that the formulations of fenofibrate and fenofibric acid that are currently available vary substantially in relation to food effect, equivalency on a milligram-to-milligram basis, and indication to be coadministered with a statin.

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Section: Resultsmentioning

confidence: 99%

A Review of Currently Available Fenofibrate and Fenofibric Acid Formulations

Ling

2013

Cardiol Res

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“…Patients with the metabolic syndrome (MS) often have atherogenic dyslipidemia, characterized by elevated triglyerides (TG) and TG-rich lipoprotein remnants, reduced highdensity lipoprotein cholesterol (HDL-C), and elevated numbers of small, dense, low-density lipoprotein (LDL) particles. [1][2][3] This lipid profile is associated with substantial elevation in coronary heart disease (CHD) event risk. 2,3 The present trial, the Triglyceride Reduction in Metabolic Syndrome (TRIMS) study, was designed to assess effects of fenofibrate therapy on atherogenic dyslipidemia and other cardiovascular risk markers in patients with hypertriglyceridemia (≥ 300 and < 1000 mg/dl) and the MS.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] This lipid profile is associated with substantial elevation in coronary heart disease (CHD) event risk. 2,3 The present trial, the Triglyceride Reduction in Metabolic Syndrome (TRIMS) study, was designed to assess effects of fenofibrate therapy on atherogenic dyslipidemia and other cardiovascular risk markers in patients with hypertriglyceridemia (≥ 300 and < 1000 mg/dl) and the MS.…”

Section: Introductionmentioning

confidence: 99%

Effects of fenofibrate on atherogenic dyslipidemia in hypertriglyceridemic subjects

Davidson

Bays

Stein

et al. 2006

Clinical Cardiology

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SummaryBackground: The metabolic syndrome (MS) is often accompanied by atherogenic dyslipidemia, which is characterized by elevated triglycerides (TG), reduced high-density lipoprotein cholesterol (HDL-C), and elevated numbers of small, dense low-density lipoprotein (LDL) particles.Hypothesis: It was hypothesized that a threshold exists for the circulating TG level needed to produce changes in LDL subclass distribution.Methods: Hypertriglyceridemic (TG ≥ 300 and < 1000 mg/dl) subjects with the MS were randomly assigned to placebo (n = 50) or 130 mg/day of micronized fenofibrate-coated microgranules (n = 96) for 8 weeks.

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“…Thus, FA might also exhibit high dermal exposure in humans as observed in rats. On the other hand, in humans, there appeared to be interindividual variability in PK, efficacy, and safety profiles of orally administered FF owing to the effect of food intake (Davidson et al, 2005). Yun et al (2006) demonstrated that the oral administration of FF with a high-fat meal can cause significant increases in C max and AUC 0-' of FA compared with those under fasted conditions in humans; hence, the effect of food intake, especially high-fat meals, might have a major effect on the photosafety of oral FF therapy since dermal exposure of FA might be increased when FF is orally taken with high-fat meals.…”

Section: Discussionmentioning

confidence: 99%

New Photosafety Assessment Strategy Based on the Photochemical and Pharmacokinetic Properties of Both Parent Chemicals and Metabolites

et al. 2015

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Photoreactivity and dermal/ocular deposition of compounds have been recognized as key considerations for evaluating the phototoxic risk of compounds. Because some drugs are known to cause phototoxic reactions via generation of potent phototoxic metabolites, photosafety assessments on parent drugs alone may lead to false predictions about their photosafety. This study aimed to establish a new photosafety assessment strategy for evaluating the in vivo phototoxic potential of both a parent substance and its metabolites. The in vivo phototoxic risk of fenofibrate (FF) and its metabolites, fenofibric acid (FA) and reduced fenofibric acid, were evaluated based on photochemical and pharmacokinetic analyses. FF and FA exhibited intensive UV absorption, with molar extinction coefficient values of 17,000 (290 nm) and 14,000 M 21 cm 21 (295 nm), respectively. Superoxide generation from FA was significantly higher than from FF, and a marked increase in superoxide generation from FF was observed after incubation with rat hepatic S9 fractions, suggesting enhanced photoreactivity of FF after metabolism. FA showed high dermal/ocular deposition after oral administration (5 mg/kg, p.o.) although the concentration of FF was negligible, suggesting high exposure risk from FA. On the basis of these findings, FA was deduced to be a major contributor to phototoxicity induced by FF taken orally, and this prediction was in accordance with the results from in vitro/in vivo phototoxicity tests. Results from this study suggest that this new screening strategy for parent substances and their metabolites provides reliable photosafety information on drug candidates and would be useful for drug development with wide safety margins.

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Efficacy and safety profile of fenofibrate-coated microgranules 130 mg, with and without food, in patients with hypertriglyceridemia and the metabolic syndrome: An 8-week, randomized, double-blind, placebo-controlled study

Cited by 11 publications

References 24 publications

A Review of Currently Available Fenofibrate and Fenofibric Acid Formulations

A Review of Currently Available Fenofibrate and Fenofibric Acid Formulations

Effects of fenofibrate on atherogenic dyslipidemia in hypertriglyceridemic subjects

New Photosafety Assessment Strategy Based on the Photochemical and Pharmacokinetic Properties of Both Parent Chemicals and Metabolites

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