Dimercaptosuccinic酸(succimer;DMSA)无机铅中毒。
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Bradberry年代,淡水河谷
Dimercaptosuccinic酸(succimer;DMSA)无机铅中毒。
中国Toxicol(费拉)。2009年8月,47(7):617 - 31所示。doi: 10.1080 / 15563650903174828。
- PubMed ID
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19663612 (在PubMed]
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简介:本文评论数据的有效性succimer (dimercaptosuccinic酸,DMSA)人类无机铅中毒的治疗,和其使用相关联的不利影响,总结了目前对药代动力学和药效学方面的理解。Toxline,方法:Medline和Embase搜索和912篇论文被识别和考虑。药物动力学和药效学:DMSA口服后吸收迅速但不完全,可能通过一个活跃的运输车。有证据表明,肝肠循环发生。大多数DMSA在血浆蛋白(以白蛋白为主)通过半胱氨酸的二硫键绑定;只有少量存在免费药物,然后在肾小球过滤广泛吸收成近端小管细胞。Nonfiltered蛋白结合的管周毛细血管DMSA也供活跃吸收成近端小管细胞基底膜阴离子运输。DMSA因此积累在肾脏广泛代谢在人类混合半胱氨酸的二硫。一些口头的10 - 25%服用剂量DMSA尿液中,大多数在24 h和大多数(> 90%)二硫化DMSA-cysteine共轭。尚不清楚是否蛋白结合的DMSA可以螯合领导; there is evidence that the mixed disulfides of cysteine are the active chelating moiety in humans. If this is the case, this suggests that chelation occurs principally, if not exclusively, in the kidney. DOSE: DMSA 30 mg/kg/day is more effective than either 10 or 20 mg/kg/day in enhancing urine lead excretion. DURATION OF THERAPY: Initial clinical studies with DMSA involved the administration of a 5-day course of treatment. Subsequently, a 19- to 26-day regimen was introduced with the intent of preventing or at least blunting a rebound in the blood lead concentration. Studies suggest, however, that repeated courses of DMSA 30 mg/kg/day for at least 5 days are equally efficacious if a treatment-free period of at least 1 week between courses is included to allow redistribution of lead from bone to soft tissues and blood. There is also evidence that in more severely poisoned patients DMSA 30 mg/kg/day can be given for more than 5 days with benefit. EFFICACY: DMSA 30 mg/kg/day significantly increases urine lead elimination and significantly reduces blood lead concentrations in lead-poisoned patients, though there is substantial individual variation in response. Over a 5-day course, mean daily urine lead excretion exceeds baseline by between 5- and 20-fold and blood lead concentrations fall to 50% or less of the pretreatment concentration, with wide variation. Maximum enhancement of urine lead elimination typically occurs with the first dose. Most symptomatic patients report improvement after 2 days of treatment. However, DMSA did not improve cognition in children < 3 years old with mild lead poisoning, presumably because lead-induced neurological damage occurred during development in utero and/or early infancy. DMSA IN PREGNANCY AND IN THE NEONATE: DMSA is not teratogenic but did produce maternal toxicity (decreased weight gain) and fetotoxicity when given in high dose (100-1,000 mg/kg/day) in experimental studies. For this reason sodium calcium edetate is generally preferred in pregnancy. ADVERSE EFFECTS: A transient modest rise in transaminase activity during chelation occurs in up to 60% of patients but has not resulted in clinically significant sequelae. Skin reactions occur in approximately 6% of treated patients and are occasionally severe. DMSA also increases urine copper and zinc excretion but not to a clinically important extent. CONCLUSIONS: DMSA is an effective lead chelator that primarily chelates renal lead. It is generally well tolerated but may occasionally cause clinically important adverse effects. DMSA may now be considered as an alternative to sodium calcium edetate, particularly when an oral antidote is preferable.