Dosage prescribing and plasma oxipurinol levels in patients receiving allopurinol therapy

Summary This study examined dosage prescribing patterns and steady-state oxipurinol plasma concentrations in 66 patients receiving chronic allopurinol therapy. Most patients (65%) were taking 300 mg allopurinol daily, although renal impairment was common.Using published guidelines, it was estimated that 35% of patients were receiving excessive dosages of allopurinol. Consequently, the plasma oxipurinol concentrations were often very high (mean (SD) was 156 (109) mol·1^–1). Accumulation of oxipurinol was inversely related to renal function. Plasma concentrations of oxipurinol and urate were not significantly related. However, most patients with oxipurinol concentrations of up to 100 mol·1^–1 had urate concentrations within the normal reference range.     

Measuring prescribing improvements in pragmatic trials of educational tools for general practitioners

Randomized pragmatic trials of drugs, physician education and drug policies are needed to improve pharmacosurveillance and cost-effectiveness of prescribing. Since 1994, we have developed and tested methods for low-cost education and policy trials to improve prescribing in primary care in Canada. We review methodology for using drug claims and other health services data to evaluate prescribing improvement programs and policies. We apply the lessons to a proposed trial of physician education tools (PET) for quality improvement of prescribing. Design issues for the trial include defining the potential programme in causal terms using counterfactuals, narrowing the denominator to the population affected, excluding noise from the numerator, calculating the prescribing preference, adjusting for baseline differences, controlling for modifiers and confounders, accounting for uncertainty when measuring impacts, and grouping practices for feedback and recognition. Data from a randomized trial of academic detailing illustrate measurement challenges. A decade of progress on methods for evaluating prescribing improvement programs with drug claims data has enabled planning of routine randomized pragmatic trials of education and policies in primary care in Canada.     

The inhibitory effects of allopurinol on the production and cytotoxicity of tumor necrosis factor

Allopurinol, a xanthine oxidase inhibitor, impaired the cytotoxic effect of human recombinant tumor necrosis factor (TNF) against WEHI cells. Actinomycin D abolished the inhibition of cytotoxicity by allopurinol. Allopurinol also exerted an inhibitory effect on the production of TNF by human mononuclear cells stimulated by either heat-killed Staphylococcus aureus or E. coli lipopolysaccharide. It is suggested that allopurinol inhibits TNF cytotoxicity by decreasing the level of oxygen free radicals generated (among other mechanisms) by the action of xanthine oxidase. Whatever the mechanism, the fact that allopurinol counteracts the toxicity of TNF can help towards an understanding of the complex nature of TNF toxicity. Correspondence to: Y. Mándi at the above address     

Relationship between physician specialty and allopurinol prescribing patterns: a study of patients with gout in managed care settings

Abstract

Objective:

Allopurinol is used to lower serum uric acid (sUA) levels in gout patients. The objective of this study was to investigate the influence of physician specialty on allopurinol treatment patterns and sUA control.     

硒和别嘌呤醇对镧损伤小鼠肝的保护作用

小鼠iv LaCl_3 7.5 mg/kg使肝发生明显损伤,ALT显著升高;光镜下见肝细胞变性,PAS染色显示糖原减少或消失;电镜下见胞浆中含许多脂滴,线粒体凝缩,内质网扩张、断裂,粗面内质网上的核糖小体脱落;血清脂质过氧化物水平显著升高。iv LaCl_3前预先给APL或Se保护的动物,ALT的升高程度显著地受到阻抑,光镜和电镜下均见肝细胞的损伤明显减轻,血清脂质过氧化物水平显著降低。结果表明APL和Se对镧引起的肝损伤均有保护作用,可能与它们能降低血清脂质过氧化物的作用有关。     

Comparison of therapeutic interchange with standard educational tools for influencing fluoroquinolone prescribing.

The abilities of therapeutic interchange (TI) and standard educational tools (SET) to change prescribing habits were compared. We evaluated the replacement of ciprofloxacin with levofloxacin in a four-hospital health system during a 14-month study period. Two hospitals used TI and two SET. The demographics, sites of infection, and severity of illness were analyzed for 554 patients treated at SET hospitals and 1323 patients treated at TI hospitals during a total of 2040 hospitalizations over a 14-month period. In TI hospitals, 97% of patients received levofloxacin, whereas 43% received levofloxacin in SET hospitals (p < 0.001). Clinical outcomes were not significantly different for the two groups, although more patients in the SET hospitals received combination antimicrobial therapy. Differences in savings per patient were significant between TI hospitals ($60) and SET hospitals ($37) (p < 0.001). The total annualized savings for all four hospitals was $156,444. TI was more effective than SET in facilitating changes in prescribing patterns in a health care system and resulted in significant cost savings to hospitals and payers.     

Enhancement of anti-inflammatory effects of calcium channel blockers by allopurinol and dimethylsulphoxide

The effects of the calcium channel blockers, nifedipine, verapamil and flunarizine, and the antioxidants, allopurinol and dimethylsulphoxide, were investigated on carrageenan-induced rat paw oedema and changes in vascular permeability. Paw volume was measured by using a plethysmometer and vascular permeability was quantified by measuring the extravasated Evans blue dye 3 h after injecting the phlogistic agent. Intraperitoneal administration of nifedipine (1,2 and 4 mg/kg), verapamil (5, 10 and 20 mg/kg), flunarizine (2.5, 5 and 10 mg/kg), allopurinol (6.25, 12.5 and 25 mg/kg) and dimethylsulphoxide (20, 40 and 80 mg/kg) 30 min before carrageenan, dose dependently inhibited oedema formation and increased vascular permeability. Co-administration of the lowest doses of calcium channel blockers with the lowest doses of antioxidants produced synergistic inhibitory effects. These results indicate that both calcium influx and oxygen-derived free radicals are involved in carrageenan-induced inflammatory responses. Thus, the synergistic effects of their combination may be due to the blockade of calcium entry and reduction in the generation of oxygen-derived free radicals.     

别嘌醇缓释胶囊对高尿酸血症大鼠胃肠和皮肤的保护作用及机制

目的:考察长期(3个月)应用别嘌醇缓释胶囊对高尿酸血症大鼠胃、肠和皮肤的影响及机制。方法:60只雄性Wistar大鼠随机分为正常对照(NC)组,模型(M)组,别嘌醇缓释胶囊低(CL)、高剂量(CH)组,别嘌醇片低(TL)、高剂量(TH)组,每组10只。除NC组,其余各组采用腺嘌呤(100mg·kg-1·d-1)和乙胺丁醇(250mg·kg-1·d-1)连续灌胃3周后改为隔日1次,共12周造成大鼠高尿酸血症。药物治疗组在造模的同时,灌胃给予别嘌醇缓释胶囊或别嘌醇片,在实验第12周末,测量各组大鼠的体质量、血尿酸和血清白细胞介素(IL)-1β含量,胃、肠和皮肤的病理改变,及皮肤中肿瘤坏死因子(TNF)-α表达情况。结果:CH组可降低高尿酸血症大鼠血尿酸水平,缓解大鼠的体质量降低(P0.01);与M和TL组,特别是TH组比较,CL和CH组可缓解大鼠胃、肠黏膜损伤;与M和TL组比较,CL和CH组降低大鼠血清IL-1β水平作用显著(P0.05);CL和CH组皮肤组织中TNF-α表达明显降低。结论:与别嘌醇片比较,长期应用别嘌醇缓释胶囊在降低血尿酸的同时表现出更好的胃、肠黏膜和皮肤保护作用;抑制TNF-α及IL-1β介导的炎症反应。