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Clin Toxicol: Dimercaptosuccinic acid (succimer; DMSA)
in inorganic lead poisoning.
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| Article Type: | Report |
| Subject: |
Succimer
(Dosage and administration) Lead poisoning (Drug therapy) Cysteine (Health aspects) |
| Authors: |
Bradberry, S. Vale, A. |
| Pub Date: | 12/01/2009 |
| Publication: | Name: Alternative Medicine Review Publisher: Thorne Research Inc. Audience: Academic; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 Thorne Research Inc. ISSN: 1089-5159 |
| Issue: | Date: Dec, 2009 Source Volume: 14 Source Issue: 4 |
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| Accession Number: | 215514488 |
| Full Text: |
INTRODUCTION: This article reviews data on the efficacy of succimer
(dimercaptosuccinic acid, DMSA) in the treatment of human inorganic lead
poisoning, the adverse effects associated with its use, and summarizes
current understanding of the pharmacokinetic and pharmacodynamic
aspects. METHODS: Medline, Toxline, and Embase were searched and 912
papers were identified and considered. PHARMACOKINETICS AND
PHARMACODYNAMICS: DMSA is absorbed rapidly but incompletely after oral
administration, probably through an active transporter. There is
evidence that enterohepatic circulation occurs. Most DMSA in plasma is
protein (mainly albumin)-bound through a disulfide bond with cysteine;
only a very small amount is present as free drug, which is filtered at
the glomerulus then extensively reabsorbed into proximal tubule cells.
Nonfiltered protein-bound DMSA in peritubular capillaries is also
available for uptake into proximal tubule cells by active anion
transport at the basolateral membrane. DMSA therefore accumulates in the
kidney where it is extensively metabolized in humans to mixed disulfides
of cysteine. Some 10-25% of an orally administered dose of DMSA is
excreted in urine, the majority within 24 h and most (>90%) as
DMSA-cysteine disulfide conjugates. It is not known whether
protein-bound DMSA can chelate lead; 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 i 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. 2009;47:617-631. |
| Gale Copyright: | Copyright 2009 Gale, Cengage Learning. All rights reserved. |