SEVERE ALLOPURINOL TOXICITY - DESCRIPTION AND GUIDELINES FOR PREVENTION IN PATIENTS WITH RENAL-INSUFFICIENCY
SEVERE ALLOPURINOL TOXICITY - DESCRIPTION AND GUIDELINES FOR PREVENTION IN PATIENTS WITH RENAL-INSUFFICIENCY
复制标题
DOI：
10.1016/0002-9343(84)90743-5
复制
发表时间：
1984-01-01
影响因子：
5.9
通讯作者：
STONE, WJ
中科院分区：
文献类型：
--
作者：
HANDE, KR;NOONE, RM;STONE, WJ
本文报告78例接受别嘌醇治疗的患者的一种危及生命的毒性综合征，包括红斑、脱皮疹、发热、肝炎、嗜酸性粒细胞增多和肾功能恶化。在大多数病例中，这种综合征的发展与肾功能不全患者使用标准剂量(200-400毫克/天)的别嘌醇有关。在药理学研究中，别嘌醇的主要代谢物--氧嘌呤的肾清除量与肌酐的肾清除量成正比(氧嘌呤清除量=0.22倍)。肌酐清除量-2.87)。血中氧嘌呤半衰期与肾肌酐清除量呈负相关([血中氧嘌呤半衰期h]-1=0.00034次。肌酐清除量，单位：毫升/分钟+0.0045)。长期使用300毫克/天的别嘌醇可导致肾功能不全患者稳态血氧嘌呤浓度升高(血氧嘌呤浓度单位：微米/L=-2.5倍)。肌酐清除量，单位：毫升/分钟+326)。根据拟议的指南，在肾功能不全患者中避免使用别嘌醇或减少剂量应足以抑制大多数患者的尿酸产生，并可能减少威胁生命的别嘌醇中毒的发生率。
A life-threatening toxicity syndrome consisting of an erythematosus, desquamative skin rash, fever, hepatitis, eosinophilia and worsening renal function in 78 patients receiving allopurinol is described. In a majority of cases, the development of this syndrome was associated with the use of standard (200-400 mg/day) doses of allopurinol in patients with renal insufficiency. In pharmacologic studies, the renal clearance of the major metabolite of allopurinol, oxipurinol, was directly proportional to the renal clearance of creatinine (oxipurinol clearance = 0.22 .times. creatinine clearance -2.87). An inverse linear relation was noted between the serum oxipurinol half-life and the renal creatinine clearance ([serum oxipurinol half-life in h]-1 = 0.00034 .times. creatinine clearance in ml/min + 0.0045). Long-term use of 300 mg/day of allopurinol resulted in elevated steady-state serum oxipurinol concentrations in patients with renal insufficiency (serum oxipurinol concentration in .mu.m/l = -2.5 .times. creatinine clearance in ml/min + 326). Avoidance of allopurinol or use of reduced doses in patients with renal insufficiency according to proposed guidelines should be adequate to inhibit uric acid production in most patients and may reduce the incidence of life-threatening allopurinol toxicity.