title: Monoisoamyl 2, 3-dimercaptosuccinic acid (MiADMSA) demonstrates higher efficacy by oral route in reversing arsenic toxicity: a pharmacokinetic approach.
abstract: Monoisoamyl DMSA (MiADMSA), a lipophilic chelating agent has emerged as a promising drug for the treatment of arsenic. The present study aimed at exploring the optimum dose and route of administration for achieving maximum arsenic elimination with minimal side effects. We also carried out a pharmacokinetic analysis of this drug to support arsenic chelation. Rats were exposed to arsenic (25 ppm) for 6 months and later received MiADMSA (50 or 100 mg/kg) orally and via i.p. route for 5 days. Oxidative stress parameters and arsenic levels in soft tissues, liver function test and histopathology of liver and kidney were performed. Plasma kinetic of MiADMSA (plasma-free drug and total drug) at 50 and 100 mg/kg p.o. was carried out. Arsenic exposure resulted in significant oxidative stress and hepatotoxicity. MiADMSA at 50 mg/kg dose administered orally provided about 45% and 75% protection against oxidative stress and in lowering body arsenic burden, respectively, against 25% and 40% via i.p. route. Pharmacokinetic analysis supported prolonged availability of the drug through oral administration. Collectively, these findings led us to conclude that oral administration of MiADMSA was more effective than intraperitoneal administration and that the minimum effective dose with least side effects was 50 mg/kg.
authors: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India. sjsflora@hotmail.com
authors: Swaran J S
authors: SJ
authors: Flora
authors: Smrati
authors: S
authors: Bhadauria
authors: Vidhu
authors: V
authors: Pachauri
authors: Abhishek
authors: A
authors: Yadav
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001151:Arsenic / Q000097:blood; D020261:Arsenic Poisoning / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002614:Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002908:Chronic Disease; D003300:Copper / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000096:biosynthesis; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D004113:Succimer / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015032:Zinc / Q000097:blood
chemical_list: D002614:Chelating Agents; D003300:Copper; C091888:monoisoamyl-2,3-dimercaptosuccinate; D004113:Succimer; D005978:Glutathione; D015032:Zinc; D001151:Arsenic; D019803:Glutathione Disulfide