In-vitro/in-vivo correlation of the nature of excreted species after chelation therapy with 2,3-dimercaptopropane-1-sulfonic acid
Treatment of lead poisoning relies primarily on chelation therapy. The
sodium salt of (R,S)-2,3-dimercapto-l-propanesulfonic acid (DMPS, DimavalL ®)
is a water-soluble analogue of British Anti-Lewisite (BAL). Its oral dosage form is
considered effective for the diagnosis and treatment of mercury poisoning
(Aposhian et a!., 1995). In adults, therapeutically successful attempts have been
reported for the treatment of chronic lead poisoning with DMPS (Anatovskaya,
1962). In children having chronic lead poisoning, the efficacy of DMPS was noted
following a 5-day therapy (Chisholm & Thomas, 1985).
Despite its current use in chelation therapy for the treatment of lead
poisoning, detailed chemical characterization and/or investigation of the resulting
complexes has not been fully investigated. DMPS and its complexes with lead are
electro active, consequently have been investigated using electro analytical
techniques. This present work was designed with the aim of (a) investigating the
in-vitro complexing behavior of DMPS with lead at simulated physiological
conditions, (b) in-vivo investigation of the chelation therapy of low and highly
exposed subjects (workers).
Electroanalytical techniques including: Voltammetry at the Dropping
Mercury electrode, Differential Pulse Polarography (DPP), Anodic Stripping
Voltammetry (ASV), and Cathodic Stripping Voltammetry (CSV), have been
employed for investigating the complexing properties ofDMPS.
Application of the methods suggested by Deford-Hume and ShumanWoodward
for measuring stability constants of metal complexes, showed that the
formed Pb:DMPS complex could be a labile coordination complex having a
formation constant ofKf= 2.66xI04
In addition, the results demonstrated that the Pb:DMPS species was much
weaker than that formed between Pb2
+ and EDTA (Kf = 1.25xI018
). This may
indicate that the mobilized lead from soft tissues and bone after chelation may have
involved mechanisms other than complex formation.
The in-vitro results demonstrated that electroanalytical techniques proved to
be highly sensitive and selective for investigating both lead as well as DMPS levels
in biological fluids. However, after chelation optimizing the media to enhance
selectivity was necessary.
Upon titration of DMPS versus lead or alternatively lead versus DMPS, the
results showed that lead did not form a stable coordination complex. However, a
compound with enough stability was formed which mobilized lead from body
stores as demonstrated by levels of lead in urine measured after a single oral dose
of DMPS (100 mg/ 3 capsules). Additionally, after dosing of exposed subjects
classified as having low and high lead body burden, in-vivo findings showed that
lead was substantially chelated after dosing with 100 mg DMPS/ 3 capsules.
However, the lead-DMPS complex was not detected in urine and hence was
regarded as a labile coordination complex. The latter finding compared well with