Determination and metabolism of dithiol chelating agents. IV. Urinary excretion of meso-2,3-dimercaptosuccinic acid and mercaptosuccinic acid in rabbits given meso-2,3-dimercaptosuccinic acid.
The water-soluble dithiol chelating agents meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid (DMPS) are becoming of increasing importance for the treatment of lead, arsenic and mercury poisoning. There is, however, a paucity of data about their metabolic transformation. Male rabbits were given DMSA (0.20 mmol/kg) i.m., and urine was collected over a 6-hr period. Monobromobimane derivatization, HPLC separation, and fluorescence detection, along with [U-14C]DMSA data, demonstrated that the total 14C found in the urine was distributed as 73% unaltered DMSA, 7% mercaptosuccinic acid and 6 and 14% of two unknowns. Electrolytic reductive treatment of the urine did not increase the urinary content of DMSA, indicating that oxidative biotransformation is not a major pathway for DMSA in the rabbit. This latter result is strikingly different from that for DMPS in rabbit.
Maiorino
R M
RM
Department of Molecular and Cellular Biology, University of Arizona, Tucson 85721.
Aposhian
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HV
D000818:Animals; D001673:Biodegradation, Environmental; D002614:Chelating Agents / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D007273:Injections, Intramuscular; D008297:Male; D011817:Rabbits; D012737:Sex Factors; D012997:Solvents; D004113:Succimer / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D013438:Sulfhydryl Compounds / Q000493:pharmacokinetics*; D013870:Thiomalates / Q000652:urine*; D014494:Unithiol / Q000493:pharmacokinetics
D002614:Chelating Agents; D012997:Solvents; D013438:Sulfhydryl Compounds; D013870:Thiomalates; D014494:Unithiol; C046062:2-thiomalic acid; D004113:Succimer