The effects of succimer on the absorption of lead in adults determined by using the stable isotope 204Pb.
The chelating agent succimer (meso-2,3-dimercaptosuccinic acid) is orally effective at inducing a urinary lead diuresis and a decrease in blood lead levels in lead poisoned children and adults. However, there are concerns that succimer may increase the absorption of lead from the gastrointestinal (GI) tract during treatment, particularly in cases of continuing lead exposure, which would compromise its effectiveness in reducing whole body lead stores. This preliminary study investigated the effects of succimer on the absorption of lead in adults using a stable lead isotopic tracer (204Pb). Twelve male subjects were divided into control (no succimer), 10, and 30 mg succimer/kg body wt treatment groups of 4 individuals each. All subjects ingested a single tracer dose (200 micrograms) of 204Pb, followed by a single oral dose of placebo (control) or succimer. Whole blood was collected at intervals of 0, 2, 4, and approximately 26 hr following ingestion of the 204Pb tracer, and composite urine and feces samples were collected over the duration of the study (approximately 26 hr). Mean intestinal excretion of 204Pb was reduced in the succimer-treated groups compared to the control (placebo), whereas urinary diuresis of 204Pb was higher in the succimer groups. The amount of lead 204Pb tracer accounted for at the end of the study was lower in the succimer-treated groups. These results suggest that GI lead absorption was enhanced by succimer and that succimer mediated the redistribution of lead from the circulation to other tissues. However, none of the differences between treatment groups were statistically significant (P < 0.05, t test) because of the relatively large within-group variability. This study demonstrates the utility of microgram doses of a stable lead isotopic tracer to assess the efficacy of clinical chelating agents in humans. Future studies are necessary to further clarify the effects of succimer on the absorption and retention of lead in adults and children. Although, based upon these preliminary data, it appears advisable that patients be maintained in a lead-safe environment while being treated with succimer.
Smith
D R
DR
Laboratory Medicine, University of California, San Francisco 94143-0843.
Markowitz
M E
ME
Crick
J
J
Rosen
J F
JF
Flegal
A R
AR
D000328:Adult; D001842:Bone and Bones / Q000737:chemistry; D004311:Double-Blind Method; D005243:Feces / Q000737:chemistry; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007554:Isotopes; D007854:Lead / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D008875:Middle Aged; D004113:Succimer / Q000494:pharmacology*
D007554:Isotopes; D007854:Lead; D004113:Succimer