Dose-response study of oral 2,3-dimercaptosuccinic acid in children with elevated blood lead concentrations.
2,3-Dimercaptosuccinic acid (DMSA) is an orally effective orphan drug that is more specific and has a wider therapeutic index than other currently available drugs used for lead intoxication. Its investigational use in the United States has been limited to the treatment of men with occupational plumbism. Twenty-one children with blood lead concentrations of 31 to 49 micrograms/dl, who also had a positive calcium disodium edetate (CaNa2EDTA) mobilization test result, were hospitalized for 7 days. Fifteen children were randomly assigned to three groups that received either 350, 700, or 1050 mg/m2/day, respectively, of DMSA in three divided doses daily. A fourth group of six children received conventional treatment with 1000 mg/m2/day of intravenously administered CaNa2EDTA in two divided doses daily. The 1050 mg/m2/day dose of DMSA was significantly more effective than lower doses of DMSA or intravenously administered CaNa2EDTA in reducing blood lead levels and restoring erythrocyte delta-aminolevulinic acid dehydratase activity. Intravenously administered CaNa2EDTA significantly increased the urinary excretion of several essential minerals (zinc, copper, iron, and calcium), whereas DMSA did not. The DMSA was well tolerated and appears extremely promising as a drug that will simplify the management of childhood lead poisoning.
Graziano
J H
JH
Department of Pharmacology, Columbia University College of Physicians and Surgeons, New York, NY 10032.
Lolacono
N J
NJ
Meyer
P
P
D000284:Administration, Oral; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004492:Edetic Acid / Q000008:administration & dosage; D006801:Humans; D007855:Lead Poisoning / Q000097:blood* / Q000652:urine; D008903:Minerals / Q000652:urine; D011897:Random Allocation; D012680:Sensitivity and Specificity; D004113:Succimer / Q000008:administration & dosage*; D013438:Sulfhydryl Compounds / Q000008:administration & dosage*
D008903:Minerals; D013438:Sulfhydryl Compounds; D004492:Edetic Acid; D004113:Succimer