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

Abstract

<jats:p> 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. </jats:p><jats:p> 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. </jats:p><jats:p> 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<jats:sup>-1</jats:sup> and three-fold less than total body clearance (391 h<jats:sup>-1</jats:sup>). The apparent volume of distribution was 211 kg<jats:sup>-1</jats:sup>. </jats:p><jats:p> 3 Post-mortem tissue analysis showed an ubiquitous colchicine distribution. Colchicine accumulated at high concentrations in the bone marrow (more than 600 ng g<jats:sup>-1</jats:sup>), testicle (400 ng g<jats:sup>-1</jats:sup>), spleen (250 ng g<jats:sup>-1</jats:sup>), kidney (200 ng g<jats:sup>-1</jats:sup>), lung (200 ng g<jats:sup>-1</jats:sup>) and heart (95 ng g <jats:sup>-1</jats:sup>); it was also found in the brain (125 ng g<jats:sup>-1</jats:sup>). </jats:p><jats:p> 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. </jats:p>

Direct Effects of Colchicine on Myocardial Function

“…It is difficult to estimate tissue concentration; however, in human myocardium, colchicine may be concentrated from 2 to 20 times more than levels in plasma. 24 At the doses used, it was found that colchicine did not prevent failure.…”

A Fatal Case of Autumn Crocus (Colchicum Autumnale) Poisoning in a Heifer: Confirmation by Mass-Spectrometric Colchicine Detection

“…18 In a study of acute human colchicines overdoses, the toxicokinetic profile of colchicine was characterized by a short distribution half-life of 30-90 min, a large volume of distribution of up to 21 l/kg body weight, and a terminal plasma half-life ranging from 10.6 hr to 31.7 hr. 17 These parameters indicate strong tissue binding with low circulating blood concentrations of the compound. An oral colchicine dose of 0.5 mg/kg body weight causes gastrointestinal symptoms in humans, whereas a dose exceeding 0.8 mg/kg leads to multiple organ failure.…”

Colchicine-induced toxicity in a heart transplant patient with chronic renal failure

“…A dose-related adverse effect of colchicine is Colchicine-induced toxicity 829 myelosuppression, most notably neutropenia. Other manifestations of colchicine toxicity include renal failure, hepatic damage, polyneuropathy, myopathy, rhabdomyolysis and cardiovascular effects including heart failuar and ventricular arhythmias (16)(17)(18)colchicine have been reported to be 7 to 60 milligrams (19) and dosages of 0.5 to 0.8 mg/kg may be fatal (20,21). Because of the large apparent volume of distribution, rapid tissue distribution, and high affinity binding at intracellular sites, colchicine is not effectively removed by hemodialysis.…”