Uricosuric Effect of Fenofibrate in Healthy Volunteers

Desager, Jean‐Pierre; Hulhoven, R.; Harvengt, C.

doi:10.1002/j.1552-4604.1980.tb01670.x

Cited by 47 publications

(26 citation statements)

References 6 publications

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“…The decrease of serum uric acid levels concomitant with the increase of uric acid clearance indicates that fenofibrate reduces serum uric acid levels by enhancing the urinary excretion of uric acid, as previously reported (7,8).…”

Section: Gout and Hyperuricemia Were Associated With Hyperlipidemia Isupporting

confidence: 84%

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Effect of Fenofibrate on Uric Acid Metabolism and Urate Transporter 1

et al. 2010

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Section: Gout and Hyperuricemia Were Associated With Hyperlipidemia Isupporting

confidence: 84%

“…Since approximately 1980, fenofibrate, a fibrate-type antihyperlipidemia drug, has been reported to decrease the serum concentration of uric acid via an enhanced urinary excretion of uric acid (7,8), but the detailed mechanism has remained unclear. Recently, Enomoto et (9).…”

Section: Hyperuricemia Frequently Is Associated With Hypertension Andmentioning

confidence: 99%

Effect of Fenofibrate on Uric Acid Metabolism and Urate Transporter 1

et al. 2010

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“…Calcium channel blockers and losartan are mildly uricosuric, unlike β blockers and other angiotensin II receptor antagonists, and both have been associated with a significant ly reduced risk of incident gout in a community based case control study. 88 The lipid lowering agent fenofibrate 89 and statins 90 are also mod estly uricosuric and should be considered when prescribing treatment for hyperlipidemia in pa tients with gout. Losartan (50 mg/d) and feno fibrate (300 mg/d) both had some additional Conclusions Surprisingly, the recommendation to eliminate urate crystals through lifelong low ering of SU below a target level, which is one of the overarching EULAR principles, and a key rec ommendation in all guidelines for the manage ment of gout from international rheumatology societies, 6,65,92,93 has recently been challenged in a clinical practice guideline from the American College of Physicians (ACP).…”

mentioning

confidence: 99%

Current management of gout: practical messages from EULAR 2016 guidelines

Nuki¹,

Doherty²,

Richette³

2017

Polish Archives of Internal Medicine

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REVIEW ARTICLE Current management of gout: practical messages from 2016 EULAR guidelines 267 where these differ significantly from the earli er guidelines and other recent national and in ternational recommendations for the manage ment of gout.Why do we need updated recommendations? There were at least half a dozen good reasons why the EULAR recommendations needed to be up dated in 2016. 1 Knowledge of the pathophysiology of uric acid (UA) transport, urate crystal inflammation, and the comorbidities associated with gout had ad vanced considerably. 2 New pharmaceutical options had become available and the evidence base for the efficacy and safety of available drugs had expanded in the last decade. 3 The incidence, prevalence, and severity of gout had continued to increase 7 despite the availability Introduction Gout is a chronic crystal deposition disorder in which crystals of monosodium urate can cause chronic arthritis, tophi, urolithiasis and renal disease, as well as recurrent acute arthritis and bursitis. Gouty arthritis and tophi can lead to chronic disability and impairment of health related quality of life, 1 but gout is also frequently associated with comorbidities such as obesity, di abetes mellitus, hypertension, and cardiovascular disease, 2,3 as well as with increased mortality. 3,4 The ABSTRACTThe European League Against Rheumatism published updated recommendations for the management of gout in 2016, comprising 3 overarching principles and 11 key recommendations for clinical practice. Patient education about the pathophysiology of gout and its comorbidities, as well as the existence of effective treatments are important, and understanding the principles of managing acute attacks and eliminating urate crystals by lifelong lowering of the serum urate (SU) below a target level are essential. Advice about lifestyle, diet, weight, and other risk factors, as well as the need to screen for and manage comorbidities are emphasized. For the treatment of flares, colchicine, nonsteroidal anti -inflammatory drugs (NSAIDs), and oral or intraarticular steroids, or a combination thereof, are recommended. In patients with frequent flares and contraindications to colchicine, NSAIDs, and corticosteroids, an interleukin -1 blocker should be considered. Urate -lowering therapy (ULT) should be discussed from the first presentation of the disease, and SU levels should be maintained at less than 6 mg/dl (360 µmol/l), or less than 5 mg/dl (300 µmol/l) in patients with severe gout. Allopurinol is recommended as first -line ULT with dose adjustment according to renal function. If the SU target cannot be achieved with allopurinol,

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“…To analyze CA, FA and Beza by chromatography, CH 3 Validation confirmed that this LC-MS/MS assay method met our needs for metabolite quantification. The analytes and the ISs were fully separated, as shown in Figure 2.…”

Section: Lc-ms/ms Assaymentioning

confidence: 64%

“…Fibrates have been used for decades to treat dyslipidemia. Clofibrate and fenofibrate are prodrugs that are hydrolyzed to clofibric acid (CA) and fenofibric acid (FA) in vivo [1][2][3]. In contrast, gemfibrozil (Gem) and bezafibrate (Beza) are active compounds.…”

mentioning

confidence: 99%

Metabolism of fibrates by cytochrome P450s and UDP-glycosyltransferases in rat and human liver microsomes

et al. 2012

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Fibrates are widely used for the treatment of dyslipidemia. However, the contributions of the phase I and phase II metabolic pathways to the clearance of fibrates are unclear. In this study, we investigated the metabolism of gemfibrozil (Gem), clofibric acid (CA), fenofibric acid (FA) and bezafibrate (Beza) by cytochrome P450s (P450s) and UDP-glycosyltransferases (UGTs) using a substrate depletion approach. We also compared the metabolic characteristics of rat liver microsomes (RLM) and human liver microsomes (HLM). The intrinsic clearance rates mediated by P450s, UGTs and both were 172 ± 22, 643 ± 26, 798 ± 103 µL min -1 mg -1, respectively, for Gem and 43 ± 11, 88 ± 12, 119 ± 15 µL min -1 mg -1 , respectively, for CA in RLM. The fractions metabolized by P450s and UGTs in RLM were 22% and 81% for Gem, 36% and 74% for CA. The P450-and UGT-mediated depletion rates for Gem were 303 and 1607 nmol min -1 mg -1 in RLM versus 86 and 243 nmol min -1 mg -1 in HLM. The corresponding rates for CA were 1.1 and 1.7 nmol min -1 mg -1 in RLM versus 0.025 and 0.038 nmol min -1 mg -1 in HLM. Accordingly, both P450s and UGTs substantially contribute to the clearance of Gem and CA, with UGTs playing a greater role. To avoid under-estimating the impact of these pathways, it is necessary to measure NADPH-and UDPGA-dependent metabolism. Although the fractions of these two pathways in RLM and HLM were similar, the depletion rate of Gem and CA in RLM was higher than that in HLM. The metabolism of FA and Beza by P450s and UGTs was too low to calculate intrinsic clearance in both RLM and HLM. These results indicate that fibrates are metabolized via similar pathways in rats and humans, and it is applicable to use RLM to predict the clearance of fibrates in human.

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Uricosuric Effect of Fenofibrate in Healthy Volunteers

Cited by 47 publications

References 6 publications

Effect of Fenofibrate on Uric Acid Metabolism and Urate Transporter 1

Effect of Fenofibrate on Uric Acid Metabolism and Urate Transporter 1

Current management of gout: practical messages from EULAR 2016 guidelines

Metabolism of fibrates by cytochrome P450s and UDP-glycosyltransferases in rat and human liver microsomes

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