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Adenine phosphoribosyltransferase (APRT) deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Therapy is aimed at reducing the formation of 2,8-dihydroxyadenine by the use of a low purine diet and allopurinol [3, 15, 50, 53]. A dose of allopurinol of 5–10 mg/kg per day up to 200–300 mg per day in an adult has been reported to eliminate 2, 8-dihydroxyadenine from the urine [15]. Adenine still accumulates. Dosage of 300 mg twice daily has more recently been recommended [44]. In a patient allergic to allopurinol, Febuxostat in a dose of 80 mg daily led to significant reduction of crystalluria [54].
F
Published in Caroline Ashley, Aileen Dunleavy, John Cunningham, The Renal Drug Handbook, 2018
Caroline Ashley, Aileen Dunleavy, John Cunningham
A study found that although exposure to febuxostat and its metabolites was generally higher in subjects with increasing degrees of renal impairment, decreases in uric acid were comparable regardless of renal function.1
Crystal deposition disorders
Published in Ashley W. Blom, David Warwick, Michael R. Whitehouse, Apley and Solomon’s System of Orthopaedics and Trauma, 2017
Paul Creamer, Dimitris Kassimos
Febuxostat is an alternative inhibitor of xanthine oxidase, metabolized and excreted by the liver, so no dose adjustment appears to be necessary in patients with mild-to-moderate renal impairment. Side-effect profile and the risk of gout flares are similar to allo-purinol. It may be useful in patients with intolerance to allopurinol or who develop allopurinol hypersensitivity syndrome.
Effect of Curcumin on Serum Urate in Asymptomatic Hyperuricemia: A Randomized Placebo-Controlled Trial
Published in Journal of Dietary Supplements, 2021
Pannipa Bupparenoo, Rattapol Pakchotanon, Pongthorn Narongroeknawin, Paijit Asavatanabodee, Sumapa Chaiamnuay
Three types of drugs are currently used in practice to lower the SU level. These include uricostatic (allopurinol and febuxostat), uricosuric (probenecid, benzbromarone, sulfinpyrazone, and lesinurad), and uricolytic drugs (rasburicase and plegoticase). According to recommendation of the Thai Rheumatism Association, the first-line drug is allopurinol (Thai Rheumatism Association 2012), which inhibits xanthine oxidase, resulting in decreasing urate production. However, allopurinol-related severe cutaneous drug reaction was reported at 0.1% to 0.4%, leading to a high mortality rate of 30%. There were reports of allopurinol-induced recurrent meningoencephalitis, acute febrile neutrophilic dermatosis, and severe cholestatic liver failure (Baker and Schumacher 2010; Strilchuk et al. 2019). On the other hand, febuxostat has a high cost and is inaccessible in some circumstances. This drug also has a similar incidence of skin rashes to allopurinol and may cause elevation of liver enzymes (Strilchuk et al. 2019). In addition, uricosuric agents have limitations to use in patients with chronic kidney disease or preexisting uric acid stone. Finally, uricolytic drugs are not available in Thailand. Therefore, there is undoubtedly a treatment gap in the management of gout. A safe and lower-cost drug that can reduce SU is needed to fill this gap.
Xanthine oxidase inhibitors: patent landscape and clinical development (2015–2020)
Published in Expert Opinion on Therapeutic Patents, 2020
Jatinder Vir Singh, Preet Mohinder Singh Bedi, Harbinder Singh, Sahil Sharma
XO enzyme is a target of significant interest to the drug discovery community for the treatment of conditions related to high SUA, inflammation and oxidative damage. Allopurinol was the first drug candidate that inhibits XO enzyme and was approved by the FDA in 1966 for the treatment of hyperurecemic condition. Reported studies indicate that high starting dose of Allopurinol increases the risk of hypersensitivity syndrome along with various other side effects [116]. For patients with severe chronic renal impairment low dose of Febuxostat is the alternative treatment option [117]. After Allopurinol, Febuxostat was the second drug candidate got approved by the FDA for treatment of high SUA. But in 2019, the FDA issued a ‘Boxed warning’ for the increased risk of heart-related issues with this drug. However, the mechanism of its cardiac toxicity is not clear so far [118,119]. After the warning issued by FDA, World Health Organization (WHO) also warned the prescribers all over the globe that Febuxostat is to be used only if the other drug fails to control the patient’s condition. In that way, Allopurinol is still a frontline option of current drug therapy for the treatment of hyperuricemia and gout. Although, novel XO inhibitors are still urgently needed to fulfil the clinical demand for this condition.
Recent approaches to gout drug discovery: an update
Published in Expert Opinion on Drug Discovery, 2020
Naoyuki Otani, Motoshi Ouchi, Hideo Kudo, Shuichi Tsuruoka, Ichiro Hisatome, Naohiko Anzai
Allopurinol is widely available and affordable. However, its effects against hyperuricemia is less than optimal, even more in patients with CKD. While both the American College of Rheumatology (ACR) [94] and European League Against Rheumatism (EULAR) [95] recommend allopurinol as a first-line urate-lowering therapy, for dosing guidance the, ACR suggests a gradual dose increase even in patients with CKD [94], while EULAR and the Japanese Society of Gout and Uric & Nucleic Acid recommend dose restriction based on creatinine clearance [89]. Some studies have reported that allopurinol dose increase above creatinine clearance-based doses is effective in maintaining serum urate levels and is well tolerated [96,97]. Febuxostat and topiroxostat can be used in patients with renal impairment without dose adjustment, and especially topiroxostat can be used safely in patients with CKD. Febuxostat should be used with caution because it may increase the risk of cardiovascular disease and mortality. There is not yet sufficient clinical data on topiroxostat. Uricolytic agents have been improved by PEGylation and other techniques. However, the number of times they can be administered is limited due to antibody formation, and the adverse events, along with the cost, are disadvantages.