Oral succimer decreases the gastrointestinal absorption of lead in juvenile monkeys

Although succimer (Chemet, meso-2,3-dimercaptosuccinic acid, DMSA) is consi dered to be a safe and effective chelating agent for the treatment of lead poisoning in humans, there is concern that it may increase the gastrointest inal (GI) absorption and retention of Pb from exposures suffered concurrent with treatment. This concern is justified because the availability of Pb-s afe housing during outpatient treatment with oral succimer is limited. We u sed a juvenile nonhuman primate model of moderate childhood Pb intoxication and a sensitive double stable Pb isotope tracer methodology to determine w hether oral succimer chelation affects the GI absorption and whole-body ret ention of Pb. Infant rhesus monkeys (n = 17) were exposed to Pb daily for 1 year postpartum to reach and maintain a target blood lead (BPb) level of 3 5-40 mug/dL. Animals were administered succimer (n = 9) or vehicle (n = 8) over two successive 13 day succimer treatment regimens beginning at 53 and 65 weeks of age. The present study was conducted over the second chelation regimen only. Animals received a single intravenous (iv) dose of stable Pb- 204 tracer 15 mug, 24.5 nmol) followed by a single oral dose of stable Pb-2 06 tracer (72.6 mug, 352 nmol) immediately before chelation, in order to sp ecifically evaluate GI Pb absorption and whole-body Pb retention with treat ment. We collected complete urine and fecal samples over the first 5 days a nd whole blood over the first 8 days of treatment for analyses of stable Pb isotopes using magnetic sector inductively-coupled plasma mass spectrometr y. Results indicate that succimer significantly reduced the GI absorption o f Pb (vehicle, 64.9% +/- 5.5; succimer, 37.0% +/- 5.8; mean +/- SEM). Succi mer also significantly increased the urinary excretion of endogenous Pb by approximately 4-fold over the vehicle treatment, while endogenous fecal Pb excretion was decreased by approximately 33%. finally, although succimer re duced the whole-body retention of endogenous Pb by approximately 10% compar ed to vehicle, the majority (77%) of the administered internal dose of Pb t racer was retained in the body when assessed after 5 days of treatment. The se data do not support the concern that succimer treatment increases GI Pb absorption.