Human studies with the chelating agents, DMPS and DMSA.
Meso-2,3-dimercaptosuccinic acid (DMSA) is bound to plasma albumin in humans and appears to be excreted in the urine as the DMSA-cysteine mixed disulfide. The pharmacokinetics of DMSA have been determined after its administration to humans po. For the blood, the tmax and t1/2 were 3.0 h + 0.45 SE and 3.2 h + 0.56 SE, respectively. The Cmax was 26.2 microM + 4.7 SE. To determine whether dental amalgams influence the human body burden of mercury, we gave volunteers the sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (DMPS). The diameters of dental amalgams of the subjects were determined to obtain the amalgam score. Administration of 300 mg DMPS by mouth increased the mean urinary mercury excretion of subjects over a 9 h period. There was a positive correlation between the amount of mercury excreted and the amalgam score. DMPS might be useful for increasing the urinary excretion of mercury and thus increasing the significance and reliability of this measure of mercury exposure. DMSA analogs have been designed and synthesized in attempts to increase the uptake by cell membranes of the DMSA prototype chelating agents. The i.v. administration of the monomethyl ester of DMSA, the dimethyl ester of DMSA or the zinc chelate of dimethyl DMSA increases the biliary excretion of platinum and cadmium in rats.
Aposhian
H V
HV
University Department of Molecular and Cellular Biology, University of Arizona, Tucson 85721.
Maiorino
R M
RM
Rivera
M
M
Bruce
D C
DC
Dart
R C
RC
Hurlbut
K M
KM
Levine
D J
DJ
Zheng
W
W
Fernando
Q
Q
Carter
D
D
D000328:Adult; D000814:Aniline Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D003723:Dental Amalgam / Q000009:adverse effects*; D004112:Dimercaprol / Q000737:chemistry; D006801:Humans; D008297:Male; D008628:Mercury / Q000652:urine; D008630:Mercury Poisoning / Q000188:drug therapy* / Q000209:etiology; D015394:Molecular Structure; D011485:Protein Binding; D051381:Rats; D004113:Succimer / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014494:Unithiol / Q000031:analogs & derivatives / Q000737:chemistry / Q000627:therapeutic use
D000814:Aniline Compounds; D004112:Dimercaprol; D014494:Unithiol; C050795:N,N-dimethyl-4-anisidine; D003723:Dental Amalgam; D004113:Succimer; D008628:Mercury