Effectiveness and Tolerability of 12-Week Treatment with Micronised Fenofibrate 200mg in a Drug-Monitoring Programme Involving 9884 Patients with Dyslipidaemia

Kirchgässler, Klaus U.; Schmitz, Helga; Bach, G.

doi:10.2165/00044011-199815030-00004

Cited by 22 publications

(12 citation statements)

References 13 publications

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“…This level of activity may have accounted for the lower infection rate in the clofibrate-treated group of animals observed previously (27), although inflammation-modulating effects similar to those of gemfibrozil (5) may have also contributed. Fenofibric acid, the major metabolite of fenofibrate in vivo (25), had the greatest activity of all the fibrate compounds that we tested, with activity at the nM medium concentrations seen with conventional antimalarial agents. As might have been predicted from this observation and consistent with the hypothesis that in vivo metabolism of therapeutic doses of fenofibrate generates fenofibric acid with useful antimalarial activity, the bioassay experiments showed that therapeutic plasma fenofibric acid concentrations inhibited CQ-sensitive and CQ-resistant strains of cultured P. falciparum.…”

Section: Discussionmentioning

confidence: 92%

In Vitro Antimalarial Activity and Drug Interactions of Fenofibric Acid

Wong¹,

Davis²

2012

Antimicrob Agents Chemother

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Plasmodium falciparum has developed resistance to most available treatments, underscoring the need for novel antimalarial drugs. Fibrates are lipid-modifying agents used to reduce morbidity and mortality associated with cardiovascular disease. They may have antimalarial activity through modulation of P-glycoprotein and ATP-binding cassette subfamily A member (ABC-1)-mediated nutrient transport and/or via a putative peroxisome proliferator-activated receptor alpha-like protein. We therefore examined in vitro antimalarial activities of fibrates and their interactions with chloroquine and dihydroartemisinin in chloroquine-sensitive (3D7) and chloroquine-resistant (W2mef) strains of P. falciparum using the conventional isotopic assay microtechnique. A bioassay was used to assess inhibition activities of human plasma after therapeutic fenofibrate doses. Fenofibric acid, the main metabolite of fenofibrate, was the most potent of the fibrates tested, with mean 50% inhibitory concentrations of 152 nM and 1,120 nM for chloroquine-sensitive and -resistant strains, respectively. No synergistic interaction between fibrates and chloroquine or dihydroartemisinin was observed. Plasma fenofibric acid concentrations, quantified by high-performance liquid chromatography in seven healthy volunteers after treatment (mean, 15.3 mg/liter, or 48 M), inhibited P. falciparum. BLAST analysis revealed the likely presence of an ABC-1 transporter homolog in P. falciparum. Our findings demonstrate that fenofibric acid has activity similar to the activities of conventional antimalarial drugs at concentrations well below those achieved after therapeutic doses. It may inhibit P. falciparum growth by inhibiting intracellular lipid transport.T he progressive increase in drug-resistant malaria, including the recent emergence of delayed clearance of Plasmodium falciparum after treatment with artemisinin derivatives (8,16,36), highlights the need for novel effective antimalarial drugs. One possible source is compounds which have been approved for other indications but which are found to have parasiticidal or diseasemodifying effects in malaria infection. Given prior detailed knowledge of their pharmacokinetic properties, safety, and tolerability, it is likely that such compounds can be fast-tracked through the usual drug development process. Examples that may prove to be pertinent to the treatment of human malaria are the glitazone drug rosiglitazone (4) and the 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor atorvastatin (30,31,34).Fibrates such as gemfibrozil and fenofibrate are agonists of peroxisome proliferator-activated receptor alpha (PPAR␣) that are in relatively widespread clinical use as potent lipid-modifying drugs (13). The first study of fibrates in malaria found that clofibrate directly inhibited the development of parasitemia in P. berghei-infected mice (27). Subsequent studies have provided indirect evidence that fibrates might have therapeutic potential in malaria. One study showed that fenofibrate was the only member of ...

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Section: Discussionmentioning

confidence: 92%

In Vitro Antimalarial Activity and Drug Interactions of Fenofibric Acid

Wong¹,

Davis²

2012

Antimicrob Agents Chemother

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“…Fenofibric acid (FFA, Fig. 1), the active metabolite of FBT, contributes for the reductions in total cholesterol, LDL cholesterol, apolipoprotien B, total triglycerides and triglyceride rich lipoprotein [13,14]. In addition, treatment with FBT also resulted in elevation of high-density lipoprotein (HDL) and apoproteins, viz., apoAI and apoAII.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of rosuvastatin and fenofibric acid in human plasma by LC–MS/MS with electrospray ionization: Assay development, validation and application to a clinical study

Trivedi¹,

Kallem²,

Mullangi³

et al. 2005

Journal of Pharmaceutical and Biomedical Analysis

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“…29–35 Findings from our fenofibrate and gemfibrozil groups demonstrated similar percent reductions in TG. Most patients were prescribed fenofibrate at only 67 mg daily despite the recommendation of 200 mg daily as an initial dose for hypertriglyceridemia in patients with normal renal function.…”

Section: Discussionmentioning

confidence: 69%

Over-the-counter fish oil use in a county hospital: Medication use evaluation and efficacy analysis

Tatachar

Pio

Yeung

et al. 2015

Journal of Clinical Lipidology

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BACKGROUND Little is known about the use and effectiveness of over-the-counter (OTC) fish oil supplements for triglyceride (TG) lowering. OBJECTIVES To (1) perform a medication-use evaluation (MUE) and (2) assess the efficacy of OTC fish oil. METHODS Retrospective, observational cohort study using electronic medical records and the pharmacy database from Parkland Health and Hospital System in Dallas, Texas. Parkland is a tax-supported county institution that provides patients with single-brand OTC fish oil. Two separate analyses were conducted. Six hundred seventeen patients (prescribed fish oil between July 1, 2012, and August 31, 2012) were included in the MUE analysis and 235 patients (109 fish oil, 72 fenofibrate, and 54 gemfibrozil, prescribed between January 1, 2012, and July 31, 2013) were included in the efficacy analysis. The main outcome measure for the MUE was fish oil prescribing habits including dosages and patient adherence, as defined by medication possession ratio. The main outcome measure for the efficacy analysis was change in lipids measured using the last value before fish oil treatment and the first value after fish oil treatment. RESULTS MUE: 617 patients received prescriptions for OTC fish oil. Sixty-four percent were prescribed a total daily dose of 2000 mg. Only 25% of patients were adherent. Efficacy analysis: despite being prescribed suboptimal doses, fish oil reduced TGs by 29% (95% confidence interval, 34.3–22.7). Compared with fish oil therapy, fibrate therapy resulted in a greater TG reduction: 48.5% (55.1–41.0) with fenofibrate and 49.8% (57.6–40.5) with gemfibrozil (P < 0001, both medications compared with fish oil). CONCLUSIONS Health care providers prescribe suboptimal doses of fish oil, and adherence is poor. Even at low doses (2 g/d), though, fish oil lowers TGs by 29%.

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Effectiveness and Tolerability of 12-Week Treatment with Micronised Fenofibrate 200mg in a Drug-Monitoring Programme Involving 9884 Patients with Dyslipidaemia

Cited by 22 publications

References 13 publications

In Vitro Antimalarial Activity and Drug Interactions of Fenofibric Acid

In Vitro Antimalarial Activity and Drug Interactions of Fenofibric Acid

Simultaneous determination of rosuvastatin and fenofibric acid in human plasma by LC–MS/MS with electrospray ionization: Assay development, validation and application to a clinical study

Over-the-counter fish oil use in a county hospital: Medication use evaluation and efficacy analysis

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