Appropriate dosing regimen of allopurinol in Japanese patients1

Takada, Mitsutaka; Okada, Hiroshi; Kotake, Takeshi; Kawato, Nobuyuki; Saito, Makoto; Nakai, Masatsugu; Gunji, Takeshi; Shibakawa, Masahiko

doi:10.1111/j.1365-2710.2005.00670.x

Cited by 15 publications

(10 citation statements)

References 17 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A maximum dose of 800 mg/day is permitted. However, in a Japanese study, patients achieved a therapeutic serum concentration of oxypurinol (> 4.6 mcg/mL) and a clinical response rate of > 90% at an allopurinol dose of just 100-200 mg/day [27]. Dosing in this study was based on levels of serum creatinine, not on eGFR.…”

Section: Discussionmentioning

confidence: 99%

Chronic kidney disease in gout in a managed care setting

et al. 2011

View full text Add to dashboard Cite

BackgroundTo study the prevalence of chronic kidney disease (CKD) and its impact on allopurinol dosing and uric acid control among patients with gout.MethodsThis was a retrospective study using data from a large US health plan. Claims and laboratory data were analyzed for enrollees from the health plan database from January 2002 through December 2005. Patients with gout were identified from pharmacy and medical claims data based on the presence of codes for gout medication or gout diagnosis. Severity of CKD was determined using the estimated glomerular filtration rate (eGFR). Allopurinol titration was defined as a change in average daily dose from first prescription to last prescription of ≥ 50 mg.ResultsA total of 3,929 patients were identified for inclusion in this study, 39% of whom had CKD (based on having an eGFR < 90 mL/min/1.73 m2). Subjects with CKD were older (p < 0.01) and more likely to be women (p < 0.01), had a greater number of comorbid conditions (p < 0.01), and were more likely to be prescribed allopurinol (p < 0.01) compared to those with no CKD. The average starting dose of allopurinol was lower among those with CKD, and it decreased with worsening kidney function. Among the 3,122 gout patients who used allopurinol, only 25.6% without CKD and 22.2% with CKD achieved a serum uric acid concentration of < 6.0 mg/dL (p = 0.0409). Also, only 15% of allopurinol users had an upward dose titration (by ≥50 mg), but the average increase in dose did not differ significantly between those with and without CKD.ConclusionsAbout two out of every five patients with gout in this population had CKD. Allopurinol doses were not adjusted in the majority of CKD patients. Serum uric acid control in gout was poor among patients without CKD and even worse among those with CKD.

show abstract

Section: Discussionmentioning

confidence: 99%

Chronic kidney disease in gout in a managed care setting

et al. 2011

View full text Add to dashboard Cite

show abstract

“…When renal impairment is present, the initial allopurinol dosage can be calculated based on the estimated creatinine clearance (Table 1) [3]. Optimization of individual allopurinol dosage can be done by targeting of the oxipurinol -steady state -serum concentrations [5][6][7][8][9] as advised in the product information of allopurinol [5]. Reference serum oxipurinol values which are considered therapeutic, range from 5 to 15 mg/L [9].…”

Section: Introductionmentioning

confidence: 99%

A simple method for quantification of allopurinol and oxipurinol in human serum by high-performance liquid chromatography with UV-detection

Reinders

Nijdam

Roon

et al. 2007

Journal of Pharmaceutical and Biomedical Analysis

View full text Add to dashboard Cite

show abstract

“…The allopurinol concentration was essentially within physiological range, ie, the trough serum oxypurinol concentration [Ͼ4.6 g/mL (ϭ30.2 mol/L)] approximated that achieved by a 100 to 200 mg single allopurinol administration to hyperuricemic patients. 31 Thus, our in vitro results might be applicable to clinical practice. XO activation was induced by hypoxia, LPS, hypoxia-inducible factor 1, and inflammatory cytokines like IL-1␤.…”

mentioning

confidence: 99%

Xanthine Oxidoreductase Is Involved in Macrophage Foam Cell Formation and Atherosclerosis Development

Kushiyama

Okubo

Sakoda

et al. 2012

ATVB

109

View full text Add to dashboard Cite

Objective-Hyperuricemia is common in patients with metabolic syndrome. We investigated the role of xanthine oxidoreductase (XOR) in atherosclerosis development, and the effects of the XOR inhibitor allopurinol on this process. Methods and Results-Oral administration of allopurinol to ApoE knockout mice markedly ameliorated lipid accumulation and calcification in the aorta and aortic root. In addition, allopurinol treatment or siRNA-mediated gene knockdown of XOR suppressed transformation of J774.1 murine macrophage cells, treated with acetylated LDL or very low density lipoprotein (VLDL) into foam cells. This inhibitory effect of allopurinol was also observed in primary cultured human macrophages. In contrast, overexpression of XOR promoted transformation of J774.1 cells into foam cells. Interestingly, SR-A1, SR-B1, SR-B II, and VLDL receptors in J774.1 cells were reduced by XOR knockdown, and increased by XOR overexpression. Conversely, expressions of ABCA1 and ABCG1 were increased by XOR knockdown and suppressed by XOR overexpression. Finally, productions of inflammatory cytokines accompanied by foam cell formation were also reduced by allopurinol administration. Conclusion-These results strongly suggest XOR activity and/or its expression level to contribute to macrophage foam cell formation. Thus, XOR inhibitors may be useful for preventing atherosclerosis. Key Words: atherosclerosis Ⅲ cell physiology Ⅲ cytokines Ⅲ macrophages Ⅲ xanthine oxidoreductase A relationship between serum uric acid levels and atherosclerotic disease development has been suggested. [1][2][3] In addition, there is epidemiological evidence of an association between hyperuricemia and metabolic syndrome, 1 type 2 diabetes, 4 chronic kidney diseases, 5,6 heart failure incidence in older adults, 7 and with mortality in patients undergoing percutaneous coronary intervention or with acute myocardial infarction. 8 -10 Uric acid itself reportedly functions as an antioxidant, 11 though the process of uric acid synthesis is accompanied by the generation of reactive oxygen species.Xanthine oxidoreductase (XOR) is a key enzyme in the uric acid production pathway; XOR oxidizes hypoxanthine from nucleic acid metabolites into xanthine, and xanthine into uric acid. XOR basically oxidizes a variety of purines and pterins, classified as molybdenum iron-sulfur flavin hydroxylases. XOR tissue and cellular distributions are high in the mammalian liver and intestine due to XOR-rich parenchymal cells. 12 XOR activity is low in human serum, brain, heart, and skeletal muscle, though a recent study revealed microvascular endothelial cells to be rich in XOR activity. 13 It seems that XOR does not induce harmful reactive oxygen species production under normal conditions but in pathological states such as ischemic congestive heart failure, XOR activity increases drastically and XOR localizes within CD68 positive macrophages. 14 Allopurinol, a xanthine oxidase (XO) inhibitor, has been widely used for hyperuricemia treatment. Oxypurinol, a hydroxide and the main met...

show abstract

Appropriate dosing regimen of allopurinol in Japanese patients1

Cited by 15 publications

References 17 publications

Chronic kidney disease in gout in a managed care setting

Chronic kidney disease in gout in a managed care setting

A simple method for quantification of allopurinol and oxipurinol in human serum by high-performance liquid chromatography with UV-detection

Xanthine Oxidoreductase Is Involved in Macrophage Foam Cell Formation and Atherosclerosis Development

Contact Info

Product

Resources

About