Predicting the kinetics of chelating agents in man from animal data

Journal Article · Sat Dec 31 23:00:00 EST 1988 · Health Physics; (USA)

DOI:https://doi.org/10.1097/00004032-198907001-00021· OSTI ID:7244175

Durbin, P W; Schmidt, C T ^[1]

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1. Lawrence Berkeley Lab., CA (USA)

Published data were collected on clearance of 82Br, 24Na, inulin, and the ligands CaNa2-EDTA and CaNa3-DTPA from plasma of rats, dogs, and adult men. Data were restructured to a common base and reanalyzed using a two-compartment open-system kinetic model with an outlet from plasma to urinary excretion or from interstitial fluid to deposition in tissues. This was used to obtain transfer rates, distribution volumes, renal clearance, tracer content of interstitial fluid, and cumulative urinary excretion. The validity of the approach was demonstrated by good agreement of the calculated distribution volumes and renal clearances of the selected tracers with published values obtained by other analytical methods. The values of the parameters of the plasma curves and the transfer rates for EDTA and DTPA in the animals were combined with physiological data to evaluate the kinetic parameters of those substances in man. The human kinetic parameters of the ligands predicted from rat or dog data differed, on the average, from the values calculated from human data by +/- 13 and +/- 38%, respectively. The effective concentration of EDTA or DTPA in body fluids from time of injection to complete excretion and the mean concentration for the first 360 min after injection was calculated to be about four times greater in man than in rats and 3.5 times greater than in dogs for equimolar amounts injected. Based on the pharmacokinetics of DTPA, chelation therapy immediately after an actinide accident involving inhalation or extensive skin damage will be more efficient and more effective if a fraction of the standard clinical ZnNa3-DTPA dosage is administered every few hours instead of as a single daily injection.

• OSTI ID: 7244175
• Journal Information: Health Physics; (USA), Journal Name: Health Physics; (USA); ISSN 0017-9078; ISSN HLTPA
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALI METAL ISOTOPES
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MODELS
BIOLOGICAL VARIABILITY
BROMINE 82
BROMINE ISOTOPES
CARBOHYDRATES
CARBOXYLIC ACIDS
CHELATING AGENTS
DAYS LIVING RADIOISOTOPES
DOGS
DRUGS
DTPA
EDTA
FORECASTING
GENETIC VARIABILITY
INTERMEDIATE MASS NUCLEI
INULIN
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MAN
METABOLISM
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
POLYSACCHARIDES
PRIMATES
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
RATS
RODENTS
SACCHARIDES
SECONDS LIVING RADIOISOTOPES
SODIUM 24
SODIUM ISOTOPES
TRACER TECHNIQUES
VERTEBRATES