静脉注射的药代学和药效学聚乙二醇重组哺乳动物在难治性痛风患者尿酸氧化酶。
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孙迪JS, Ganson新泽西,凯莉SJ,斯佳丽EL, Rehrig CD,黄W, Hershfield女士
静脉注射的药代学和药效学聚乙二醇重组哺乳动物在难治性痛风患者尿酸氧化酶。
关节炎感冒。2007年3月,56 (3):1021 - 8。doi: 10.1002 / art.22403。
- PubMed ID
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17328081 (在PubMed]
- 文摘
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摘要目的:评价疗效、免疫原性和耐受性的哺乳动物静脉注射(IV)聚乙二醇重组尿酸氧化酶(PEG-uricase)治疗严重的痛风。方法:单注入PEG-uricase(从0.5毫克剂量12毫克)为24例(6 4例患者群)在第一阶段的临床试验。血浆尿酸酶活性(pUox)、血浆尿酸盐浓度(pUAc)和尿酸acid-to-creatinine比率(UAc: Cr)尿液中监控加药后21天。不良事件和免疫球蛋白抗体反应PEG-uricase随访35天。结果:所有患者完成了试验。最大pUox PEG-uricase第四剂量线性相关,曲线下的面积(AUC)值线性增加(最多8毫克的剂量),和pUox半衰期为6.4 -13.8天。4 - 12毫克的剂量后,pUAc 24 - 72小时内下跌,从平均+ / - SD值11.1 + / - 0.6 mg / dl 1.0 + / - 0.5 mg / dl;的AUC值pUAc相当于维持在1.2 - -4.7 mg / dl pUAc postinfusion 21天。UAc:尿液中Cr率下降与pUAc并行。免疫球蛋白抗体PEG-uricase,大多是IgG2和具体挂钩,曾快速酶开发的9名患者的间隙,但没有过敏反应。 All adverse events were mild to moderate, with gout flares being most common. CONCLUSION: The bioavailability, efficacy, and tolerability of IV PEG-uricase were greater than the bioavailability, efficacy, and tolerability observed in a previous phase I trial of subcutaneous PEG-uricase. Infusing 4-12 mg of PEG-uricase every 2-4 weeks should maintain the pUAc well below the therapeutic target of 6 mg/dl and greatly reduce renal uric acid excretion. This treatment could be effective in depleting expanded tissue urate stores in patients with chronic or tophaceous gout.
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- 药物