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Other Drugs Used to Treat Seizures
Published in Stanley R. Resor, Henn Kutt, The Medical Treatment of Epilepsy, 2020
Allopurinol is well absorbed after oral administration. The major metabolite is oxipurinol. The biological half-life of allopurinol is around 1 hour, and that of oxipurinol is around 20 hours (13).
The Role of Neutrophils and Reactive Oxygen Metabolites in Reperfusion Injury
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
Barbara J. Zimmerman, D. Neil Granger
Inasmuch as oxygen radical scavengers afford protection in models of reperfusion injury and the intestine is a rich source of the oxygen radical-producing enzyme, much attention has been devoted to assessing the role of xanthine oxidase in intestinal reperfusion injury. The xanthine oxidase inhibitors allopurinol, oxypurinol, and pterin aldehyde have been widely used to assess the contribution of xanthine oxidase. All of the inhibitors dramatically attenuate both the epithelial cell necrosis and the increased microvascular permeability observed following reperfusion of the ischemic bowel.3,8,21 These results suggest that xanthine oxidase may be an important source of the oxidants produced at reperfusion.
Cardiovascular Disease and Oxidative Stress
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Marco Fernandes, Alisha Patel, Holger Husi
Pharmacological intervention targeting this class of proteins has shown very little promise. XO inhibitory drugs, such as Oxypurinol, administered to CVD and hyperuricaemia patients did not shown benefit. More multi-centre clinical trials with controlled randomisation and further patient stratification are required, not only to uncover the connection of uric acid with disease pathogenesis, but also with other associated functions such as assessment of renal function (Zhang J. et al., 2017).
Engineered Escherichia coli Nissle 1917 with urate oxidase and an oxygen-recycling system for hyperuricemia treatment
Published in Gut Microbes, 2022
Rui Zhao, Zimai Li, Yuqing Sun, Wei Ge, Mingyu Wang, Huaiwei Liu, Luying Xun, Yongzhen Xia
Hyperuricemia could be treated either by reducing UA production or promoting UA excretion through the kidney, which are two major factors leading to the development of hyperuricemia.6 There are four clinical treatment options. First, diet control is used to reduce the intake of purines and nucleosides.7 Second, xanthine oxidase inhibitors such as allopurinol, oxypurinol, and febuxostat, are used to inhibit the activity of xanthine oxidase to reduce UA production.8 Third, URAT1 (human urate transporter 1), which is a key UA transporter and is responsible for reabsorbing UA from the renal tubule into cells,9,10 is inhibited by drugs such as probenecid, benzbromarone, and losartan to reduce UA absorption in the renal tubules.11 Fourth, UA is degraded in the blood by supplementing exogenous UOX.12
Fabrication and characterization of dissolving microneedles for transdermal drug delivery of allopurinol
Published in Drug Development and Industrial Pharmacy, 2021
Jianmin Chen, Xinying Liu, Siwan Liu, Zemin He, Sijin Yu, Zhipeng Ruan, Nan Jin
Allopurinol (AP), a xanthine oxidase inhibitor, is well known to reduce the production of uric acid by preventing the oxidation of hypoxanthine and xanthine [1]. It has been considered as the first line drug in treating hyperuricemia and gout. Additionally, AP can also be used in the treatment of tumor lysis syndrome [2], inflammatory bowel disease [3], and chronic heart failure [4]. However, the oral drug delivery of AP is associated with severe adverse effects like allopurinol hypersensitivity syndrome (AHS) that is characterized by fever, rash, eosinophilia, and renal dysfunction, especially when a high dosage is administrated [5]. It has been reported that low starting AP dose is likely to reduce the risk of AHS [6], since the incidence and seriousness of adverse effects have been ascribed to the concentration of oxipurinol that is a dynamic metabolite of AP [7]. Besides, oral drug delivery is easily affected by the hepatic first-pass effect, resulting in a lower bioavailability of drugs. On the other hand, the poor solubility (limited solubility in both polar and nonpolar solvents) and shorter half-life (1–2 h) of AP lead to lower bioavailability of drug via the oral route [8]. Therefore, the development of sustained release formulation of AP for reducing adverse effects and enhancing bioavailability is highly desired.
Investigational drugs for hyperuricemia, an update on recent developments
Published in Expert Opinion on Investigational Drugs, 2018
Tristan Pascart, Pascal Richette
Allopurinol has an active metabolite, oxypurinol, which inhibits the conversion of hypoxanthine to xanthine and the conversion of xanthine to urate, and therefore prevents urate production [12]. Allopurinol is cheap and is the only ULT available worldwide. Allopurinol is initiated at low dose, with dosage being increased up to 800 mg in the US and 900 mg in Europe to reach the predefined SU target of 6 or 5 mg/dL in patients with normal kidney function. Serious cutaneous adverse events (SCARs), the main fear with allopurinol, strongly associated with HLA B*5801, are very rare but can be life-threatening [13,14]. In some countries, allopurinol dosage is to be adapted to the creatinine clearance to decrease this risk as renal failure is considered a risk factor for SCARs [13] limiting its use in chronic kidney disease patients. Unfortunately, physicians seldom prescribe allopurinol above 300 mg per day [15], despite recent data advocating up-titration of the drug even in case of renal impairment [16,17]. At doses below 300 mg daily, less than half of patients reach the SU target of below 6.0 mg/dL [9,18]. However, even without adjustment of allopurinol to the estimated glomerular filtration rate (eGFR), about a third of patients do not achieve SU levels below 6.0 mg/dL [19].