Randomized placebo-controlled trial of 2,3-dimercapto-1-propanesulfonate (DMPS) in therapy of chronic arsenicosis due to drinking arsenic-contaminated water.
BACKGROUND
Chronic arsenic toxicity, producing various clinical manifestations, is currently epidemic in West Bengal, India, Bangladesh, and other regions of the world. 2,3-Dimercapto-1-propanesulfonate, a chelating agent, increases excretion of arsenic in urine to several times the prechelation concentration but the therapeutic efficacy of 2,3-dimercapto-1-propanesulfonate in the management of chronic arsenic toxicity has been incompletely evaluated. We investigated the clinical use of 2,3-dmercapto-1-propanesulfonate in such patients.


METHODS
Twenty-one consecutive patients with chronic arsenicosis were individually randomized into 2 groups: 11 patients (9 males and 2 females, age 30.63+/-11.4 years) received 2,3-dimercapto-1-propanesulfonate 100-mg capsules 4 times a day for 1 week and repeated in the 3rd, 5th, and 7th week with no drug during the intervening period. The other 10 patients (5 males and 5 females, age 34.4+/-14.41 years) were given placebo capsules (resembling 2,3-dimercapto-1-propanesulfonate) in the same schedule. The consumption of arsenic-contaminated water was terminated by all 21 subjects. Initial and posttreatment urinary arsenic excretion was determined in all cases. Sequential excretion of urinary arsenic was determined during the treatment of 2 drug- and 1 placebo-treated cases. The clinical features were evaluated by an objective scoring system before and after treatment. Routine investigation including liver function test and skin biopsy were also done before and after the treatment. Drug-associated toxicity was tabulated.


RESULTS
Therapy with 2,3-dimercapto-1-propanesulfonate caused significant improvement in the clinical condition of chronic arsenicosis patients as evidenced by significant reduction of total clinical scores from 8.90+/-2.84 to 3.27+/-1.73; p < 0.0001. Exposure cessation alone with placebo treatment also reduced clinical scores (8.50+/-1.96 to 5.40+/-2.12; p < 0.003), but the posttreatment total clinical score of 2,3-dimercapto-1-propanesulfonate-treated patients (3.27+/-1.73) was significantly lower than that of placebo-treated patients (5.40+/-2.12; p < 0.01). The most significant improvement was noted in regard to the clinical scores of weakness, pigmentation, and lung disease. No difference was noted between groups in the hematological and biochemical parameters (which were normal) and skin histology before and after treatment. No 2,3-dimercapto-1-propanesulfonate-related adverse effects were noted. Total urinary excretion of arsenic in 2,3-dimercapto-1-propanesulfonate-treated cases increased significantly following drug therapy, with no increase in placebo-treated cases.


CONCLUSIONS
2,3-Dimercapto-1-propanesulfonate treatment caused significant improvement in the clinical score of patients suffering from chronic arsenic toxicity. Increased urinary excretion of arsenic during the period of therapy is the possible cause of this improvement.
Guha Mazumder
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Department of Gastroenterology and Medicine, Institute of Postgraduate Medical Education and Research, Calcutta, India. dngm@apexmail.com
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B K
BK
Santra
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A
Ghosh
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Das
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Lahiri
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Das
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D000328:Adult; D000931:Antidotes / Q000008:administration & dosage / Q000627:therapeutic use*; D001151:Arsenic / Q000652:urine; D020261:Arsenic Poisoning / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D002614:Chelating Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015913:Chelation Therapy; D002908:Chronic Disease; D004334:Drug Administration Schedule; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D016037:Single-Blind Method; D012871:Skin Diseases / Q000139:chemically induced; D013054:Spectrophotometry, Atomic; D016896:Treatment Outcome; D014494:Unithiol / Q000008:administration & dosage / Q000627:therapeutic use*; D014874:Water Pollutants, Chemical / Q000506:poisoning*; D014881:Water Supply
D000931:Antidotes; D002614:Chelating Agents; D014874:Water Pollutants, Chemical; D014494:Unithiol; D001151:Arsenic