The biological fate of sup 14 C-dimercaptosuccinic acid in monkeys and rabbits

Journal Article · Fri Sep 01 00:00:00 EDT 1989 · Military Medicine; (USA)

OSTI ID:5186780

Tillotson, J A; Boswell, G; Kincannon, L; Speckman, C L

The biological fate of {sup 14}C-labeled dimercaptosuccinic acid (DMSA) in monkeys and rabbits was determined by measuring the {sup 14}C activity in their urine, feces, and expired air ({sup 14}CO{sub 2}). Monkeys absorbed less than 20% DMSA from three oral dose levels (0.082, 0.16, and 0.5 mmol/kg) of {sup 14}C-DMSA, and the rabbits absorbed 32% DMSA or less from an oral dose of {sup 14}C-DMSA (0.5 mmol/kg). Although the bioavailability of DMSA was limited in either species, DMSA was detected in the blood of both species within minutes after oral dosing. In either species, most of the radiolabel from the absorbed {sup 14}C-DMSA was detected in the urine within 12 hours. We also developed a sensitive assay for directly measuring levels of DMSA (as free thiols) in blood. Intact DMSA was not detected in the blood of the monkeys or the rabbits more than 200 minutes after oral or intravenous dosing at 0.5 mmol DMSA/kg body weight. However, {sup 14}C activity in blood and urine of the monkeys was measurable 72 hours after this dose. Differences between measured {sup 14}C concentrations and intact DMSA concentrations in the blood suggest the presence of DMSA metabolites that have longer half-lives than DMSA. Consequently, until the biological activities of these compounds are identified, the pharmacokinetic analysis of DMSA may be incomplete.

• OSTI ID: 5186780
• Journal Information: Military Medicine; (USA), Vol. 154:9; ISSN 0026-4075
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
THIOLS
METABOLISM
BIOLOGICAL HALF-LIFE
CARBON 14 COMPOUNDS
CARBON DIOXIDE
CLEARANCE
GENETIC VARIABILITY
INTRAVENOUS INJECTION
METABOLITES
ORAL ADMINISTRATION
RABBITS
ANIMALS
BIOLOGICAL VARIABILITY
CARBON COMPOUNDS
CARBON OXIDES
CHALCOGENIDES
INJECTION
INTAKE
LABELLED COMPOUNDS
MAMMALS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
VERTEBRATES
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