Gout treatment: should we aim for rapid crystal dissolution?

Pascual, Eliseo; Andrés, Mariano; Vela, Paloma

doi:10.1136/annrheumdis-2012-202594

Cited by 25 publications

(26 citation statements)

References 37 publications

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“…1,[24][25][26][27] The current results are in line with those obtained with the combination of lesinurad and febuxostat in patients with gout, 28 where superior reductions in sUA were achieved when lesinurad 400 mg or 600 mg was administered with febuxostat 40 mg or 80 mg than when febuxostat 40 mg or 80 mg was given alone. Achieving sUA levels below recommended targets may lead to improved outcomes such as lower gout flare incidence and/or more rapid tophus area reduction.…”

Section: Discussionsupporting

confidence: 83%

“…The quantitative determination of verinurad has been reported previously (24). The quantitative determination of verinurad has been reported previously (24).…”

Section: Methodsmentioning

confidence: 97%

“…24 , cumulative amount of drug excreted unchanged in urine from time 0 to 24 hours postdose; AUC 0-24 , area under the plasma concentration-time curve from time 0 to 24 hours postdose; CI, confidence interval; CL R0-24 , renal clearance from time 0 to 24 hours postdose; C max , maximum observed plasma concentration; f e0-24 , fraction of drug excreted in urine unchanged from time 0 to 24 hours postdose; n, number of subjects with data; T max , time to maximum plasma concentration; geomean: geometric mean. a T max values represented by median (range).…”

mentioning

confidence: 99%

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Pharmacokinetics, Pharmacodynamics, and Tolerability of Concomitant Administration of Verinurad and Febuxostat in Healthy Male Volunteers

Hall¹,

Gillen

Yang³

et al. 2018

Clinical Pharm in Drug Dev

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Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in development for treatment of gout and asymptomatic hyperuricemia. This phase 1, single-blind, multiple-dose, drug-drug interaction study evaluated the pharmacokinetics (PK), pharmacodynamics, and safety/tolerability of verinurad in combination with febuxostat in healthy male volunteers. Twenty-three subjects were randomized and received once-daily doses of verinurad (or placebo) or febuxostat alone (days 1-7 and days 15-21), or verinurad + febuxostat on days 8-14. For combinations, subjects received verinurad 10 mg + febuxostat 40 mg or verinurad 2.5 mg + febuxostat 80 mg. Plasma/serum and urine samples were analyzed for verinurad, febuxostat, and uric acid. Safety was assessed by adverse events and laboratory tests. Febuxostat 40 mg had no effect on plasma exposure of verinurad 10 mg, whereas febuxostat 80 mg increased the maximum observed plasma concentration and the area under the plasma concentration-time curve of verinurad 2.5 mg by 25% and 33%, respectively. Verinurad had no effect on febuxostat PK. Maximal reduction in serum urate was 76% with verinurad 10 mg + febuxostat 40 mg versus verinurad 10 mg (56%) or febuxostat 40 mg (49%) alone and was 67% with verinurad 2.5 mg + febuxostat 80 mg versus verinurad 2.5 mg (38%) or febuxostat 80 mg (57%) alone. Verinurad increased, whereas febuxostat decreased, 24-hour fractional excretion and renal clearance of uric acid. There was no clinically significant drug-drug interaction between verinurad and febuxostat PK. The combination resulted in greater reductions of serum urate than either drug alone and was well tolerated at the studied doses.

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Section: Discussionsupporting

confidence: 83%

“…The quantitative determination of verinurad has been reported previously (24). The quantitative determination of verinurad has been reported previously (24).…”

Section: Methodsmentioning

confidence: 97%

mentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetics, Pharmacodynamics, and Tolerability of Concomitant Administration of Verinurad and Febuxostat in Healthy Male Volunteers

Hall¹,

Gillen

Yang³

et al. 2018

Clinical Pharm in Drug Dev

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show abstract

“…However, lower SUA levels result in a faster reduction of MSU crystal deposits, as has been shown in tophaceous gout [Pérez-Ruiz et al 2002b]. It therefore appears reasonable to aim for a lower SUA level, especially in severe gout [Pascual et al 2013]. Ideally, target SUA levels should be tailored according to the crystal load of the patients.…”

Section: Urate-lowering Therapiesmentioning

confidence: 99%

Gout: optimizing treatment to achieve a disease cure

Bernal

Quilis

Andrés

et al. 2016

Therapeutic Advances in Chronic Disease

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Gout is one of the most common inflammatory arthritides. The disease is due to the deposition of monosodium urate crystals. These deposits are reversible with proper treatment, suggesting that gout is a curable disease. The main aim in gout is to lower serum uric acid levels to a pre-established target; there are different urate-lowering drugs (xanthine oxidase inhibitors, uricosurics and uricases) through which this can be achieved. Proper treatment of gout also involves correct management of acute flares and their prevention. To ensure treatment adherence it is necessary to explain to the patient what the objectives are.

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“…Gout, the most prevalent form of inflammatory arthritis, is a disease primarily triggered by urate overload with arthritis as a consequence of pathological accumulation (Pascual et al, 2013). Increased serum urate concentration or hyperuricemia results in the deposition of monosodium urate crystals in and around joints, which is the major underlying pathophysiological mechanism of gout.…”

Section: Introductionmentioning

confidence: 99%

PDK2 and ABCG2 genes polymorphisms are correlated with blood glucose levels and uric acid in Tibetan gout patients

et al. 2016

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ABSTRACT. Previous studies have shown that the PDK2 and ABCG2 genes play important roles in many aspects of gout development in European populations. However, a detailed genotype-phenotype analysis was not performed. The aim of the present study was to investigate the potential association between variants in these two genes and metabolismrelated quantitative phenotypes relevant to gout in a Chinese Tibetan population. In total, 316 Chinese Tibetan gout patients were recruited from rheumatology outpatient clinics and 6 single nucleotide polymorphisms in PDK2 and ABCG2 were genotyped, which were possible etiologic variants as identified in the HapMap Chinese Han Beijing population. A significant difference in blood glucose levels was detected between different genotypes of rs2728109 (P = 0.005) in the PDK2 gene. We also detected a significant difference in the mean serum uric levels between different genotypes of rs3114018 (P = 0.004) in the ABCG2 gene. All P values remained significant after Bonferroni's correction for multiple testing. Our data demonstrate potential roles for PDK2 and ABCG2 polymorphisms in the metabolic phenotypes of Tibetan gout patients, which may provide new insights into the etiology of gout. Further studies are required to confirm these findings.

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Gout treatment: should we aim for rapid crystal dissolution?

Cited by 25 publications

References 37 publications

Pharmacokinetics, Pharmacodynamics, and Tolerability of Concomitant Administration of Verinurad and Febuxostat in Healthy Male Volunteers

Pharmacokinetics, Pharmacodynamics, and Tolerability of Concomitant Administration of Verinurad and Febuxostat in Healthy Male Volunteers

Gout: optimizing treatment to achieve a disease cure

PDK2 and ABCG2 genes polymorphisms are correlated with blood glucose levels and uric acid in Tibetan gout patients

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