Toxicokinetics of Colchicine in Humans: Analysis of Tissue, Plasma and Urine Data in Ten Cases

1 A specific and sensitive radioimmunoassay was used to study the toxicokinetics of colchicine in seven cases of acute human poisoning. Post-mortem tissue concentrations of colchicine were measured in three further cases. Depending on the time of patient admission, two disposition processes could be...

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Bibliographic Details
Published in:Human & experimental toxicology 1992-11, Vol.11 (6), p.510-516
Main Authors: Rochdi, M., Sabouraud, A., Baud, F.J., Bismuth, C., Scherrmann, J.M.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Biological and medical sciences
Colchicine - blood
Colchicine - pharmacokinetics
Colchicine - poisoning
Drug intoxications. Doping
Female
Half-Life
Humans
Male
Medical sciences
Metabolic Clearance Rate
Middle Aged
Pharmacology. Drug treatments
Radioimmunoassay
Tissue Distribution
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Summary:1 A specific and sensitive radioimmunoassay was used to study the toxicokinetics of colchicine in seven cases of acute human poisoning. Post-mortem tissue concentrations of colchicine were measured in three further cases. Depending on the time of patient admission, two disposition processes could be observed. The first, in three patients, admitted early, showed a bi-exponential plasma colchicine decrease, with distribution half-lives of 30, 45 and 90 min. The second, in four patients, admitted late, showed a mono-exponential decrease. Plasma terminal half-lives ranged from 10.6 to 31.7 h for both groups. 2 Pharmacokinetic analysis of urine colchicine data was performed for two patients. The fraction of unchanged colchicine excreted in urine was about 30%, renal clearance was about 131 h-1 and three-fold less than total body clearance (391 h-1). The apparent volume of distribution was 211 kg-1. 3 Post-mortem tissue analysis showed an ubiquitous colchicine distribution. Colchicine accumulated at high concentrations in the bone marrow (more than 600 ng g-1), testicle (400 ng g-1), spleen (250 ng g-1), kidney (200 ng g-1), lung (200 ng g-1) and heart (95 ng g -1); it was also found in the brain (125 ng g-1). 4 This toxicokinetic study shows that after massive ingestion, the disposition parameters and kinetics of colchicine are not markedly modified from those occuring in healthy volunteers. The absorption process was not delayed and the distribution and elimination half-lives were in the range known to occur with therapeutic doses.
ISSN:0960-3271
1477-0903
DOI:10.1177/096032719201100612