Safety profile of anti-gout agents

Stamp, Lisa K.

doi:10.1097/bor.0000000000000031

Cited by 34 publications

(20 citation statements)

References 48 publications

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“…Therefore, adherence to urate‐lowering therapy is a key issue in the management of gout. As documented in the medical literature, adherence to allopurinol is a major issue, which is partly related to its tolerability profile . The estimated incidence of adverse reactions ranged from 2% to 8% of users, including hypersensitivity reactions (i.e.…”

Section: Discussionmentioning

confidence: 99%

Allopurinol adherence among patients with gout: an Italian general practice database study

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Allopurinol adherence among patients with gout: an Italian general practice database study

et al. 2015

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“…Therapeutically used XO inhibitors suppress the production of uric acid, allowing for renal excretion of the uric acid precursors xanthine and hypoxanthine prior to the formation of uric acid. Allopurinol, a purine analog and prototype XO inhibitor which has been in use since 1966, is efficacious, but its relatively low potency (IC 50 : 0.2 – 50 µM; [6]) requires dosages that can cause undesirable side effects, ranging from mild gastrointestinal upset to more severe hypersensitivity reactions and renal toxicity [9–12]. Even though a number of promising alternative treatments of hyperuricemia such as recombinant uricase therapy, the use of interleukin-1 inhibitors, or the targeting of renal urate transporters are currently explored [13–15], XO inhibitors still remain first-line therapy.…”

Section: Introductionmentioning

confidence: 99%

Hydroxylated chalcones with dual properties: Xanthine oxidase inhibitors and radical scavengers

Hofmann

Webster

et al. 2016

Bioorganic & Medicinal Chemistry

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In this study, we evaluated the abilities of a series of chalcones to inhibit the activity of the enzyme xanthine oxidase (XO) and to scavenge radicals. 20 mono- and polyhydroxylated chalcone derivatives were synthesized by Claisen-Schmidt condensation reactions and then tested for inhibitory potency against XO, a known generator of reactive oxygen species (ROS). In parallel, the ability of the synthesized chalcones to scavenge a stable radical was determined. Structure-activity relationship analysis in conjunction with molecular docking indicated that the most active XO inhibitors carried a minimum of three hydroxyl groups. Moreover, the most effective radical scavengers had two neighboring hydroxyl groups on at least one of the two phenyl rings. Since it has been proposed previously that XO inhibition and radical scavenging could be useful properties for reduction of ROS-levels in tissue, we determined the chalcones’ effects to rescue neurons subjected to ROS-induced stress created by the addition of β-amyloid peptide. Best protection was provided by chalcones that combined good inhibitory potency with high radical scavenging ability in a single molecule, an observation that points to a potential therapeutic value of this compound class.

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“…Gout treatment guidelines recommend the use of colchicine, systemic corticosteroids, or NSAID for the prevention and treatment of gout flares 3,10 . While colchicine and NSAID are effective for treating flares, they are poorly tolerated or contraindicated in most patients 11 . A study indicated that > 90% of patients with gout had at least 1 contraindication to NSAID and systemic steroids, and > 30% had at least 1 contraindication to colchicine 25 .…”

Section: Rheumatologymentioning

confidence: 99%

“…Therefore, guidelines 3,10 recommend that patients initiating ULT take antiinflammatory compounds such as colchicine, systemic corticosteroids, or nonsteroidal antiinflammatory drugs (NSAID) for flare prophylaxis. These antiinflammatories are themselves poorly tolerated, potentially unsafe, and contraindicated in many patients with gout 11 . Thus, there is a pressing need for new gout treatments that provide better SUA and flare controls.…”

mentioning

confidence: 99%

The Pharmacodynamics, Pharmacokinetics, and Safety of Arhalofenate in Combination with Febuxostat When Treating Hyperuricemia Associated with Gout

Steinberg

Vince²,

Choi³

et al. 2016

J Rheumatol

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Objective.Arhalofenate (ARH), in development for gout, has uricosuric and anti-flare activities. ARH plus febuxostat (FBX) were evaluated in subjects with gout for serum uric acid (SUA) lowering, drug interaction, and safety.Methods.Open phase II trial in gout volunteers (NCT02252835). Cohort 1 received ARH 600 mg for 2 weeks, followed by sequential 1-week co-administration of FBX 80 mg followed by 40 mg. FBX 40 mg was continued alone for 2 weeks. Cohort 2 received ARH 800 mg for 2 weeks, followed by sequential 1-week co-administration of FBX 40 mg followed by 80 mg. FBX 80 mg was continued alone for 2 weeks. SUA, its fractional excretion (FEUA), and plasma oxypurines were assessed. Pharmacokinetics of FBX and ARH were determined alone and in combination for cohort 2.Results.Baseline mean SUA was 9.4 mg/dl for cohort 1 (n = 16) and 9.2 mg/dl for cohort 2 (n = 16). The largest SUA decrease (63%) was observed with ARH 800 mg + FBX 80 mg, with all subjects reaching SUA < 6 mg/dl and 93% < 5 mg/dl. The area under the curve (AUC)(0-t)of ARH acid + FBX/ARH acid was 108%. The AUC(0-t)of FBX + ARH acid/FBX was 87%. As expected, FBX increased oxypurines and increases were unaffected by ARH co-administration. Baseline FEUA were low (3.5%–4.6%) and ARH increased them toward normal without overexcretion of UA. ARH was well tolerated and appeared safe.Conclusion.ARH and FBX lowered SUA by complementary mechanisms. The combination provided greater decreases than each drug alone. The combination was well tolerated and appeared safe. Trial registration:NCT02252835.

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Safety profile of anti-gout agents

Abstract: In general, treatments for gout are well tolerated, although clinicians must keep in mind the potential for drug interactions and the contribution of comorbidities to the potential for adverse effects with gout therapies.

Cited by 34 publications

References 48 publications

Allopurinol adherence among patients with gout: an Italian general practice database study

Allopurinol adherence among patients with gout: an Italian general practice database study

Hydroxylated chalcones with dual properties: Xanthine oxidase inhibitors and radical scavengers

The Pharmacodynamics, Pharmacokinetics, and Safety of Arhalofenate in Combination with Febuxostat When Treating Hyperuricemia Associated with Gout

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