Biosynthesis and Isolation of Radioactive Colchicine

Walaszek, Edward J.; Kelsey, F. E.; Geiling, E. M. K.

doi:10.1126/science.116.3009.225

Cited by 25 publications

(8 citation statements)

References 7 publications

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“…Colchicine myopathy is a well‐described clinical entity predominantly seen in elderly patients with chronic renal insufficiency in whom hyperuricemia and flares of gouty arthritis frequently occur. This relationship reflects colchicine's renal elimination, which accounts for approximately 10–20% of its total body clearance 24. For this reason, dosing should be sensitive to renal function and clear guidelines have been published that recommend restricting colchicine treatment to patients with a creatinine clearance of ≥50 ml/min 25.…”

Section: Discussionmentioning

confidence: 99%

Cytoskeletal myotoxicity from simvastatin and colchicine

et al. 2004

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We report the case of a 79-year-old man with mild chronic renal failure who developed severe rhabdomyolysis after combined exposure to simvastatin and colchicine. Colchicine induces myopathy through disruption of microtubular function with subsequent vacuolization and pseudomyelinic body accumulation. Statin therapy is associated with myonecrosis, membranous myeloid bodies, and vacuolization, presumably as a function of impaired isoprenoid metabolism. Vesicle trafficking requires small G-protein prenylation and statins can disrupt cytoskeletal integrity. We propose that synergistic cytoskeletal myotoxicity may account for the extreme elevation of serum creatine kinase not previously reported in pure colchicine myopathy.

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Section: Discussionmentioning

confidence: 99%

Cytoskeletal myotoxicity from simvastatin and colchicine

et al. 2004

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“…Following intravenous administration, colchicine distributes widely into plasma proteins, blood cells, as well as into various tissues [15]. Studies in patients demonstrated that biliary excretion seems to be the predominant route of colchicine elimination [20]. Moreover, it has been shown that the renal clearance is 4 l/kg, representing 10% of the total body clearance [21].…”

Section: Introductionmentioning

confidence: 99%

Impact of solutol HS 15 on the pharmacokinetic behaviour of colchicine upon intravenous administration to male Wistar rats

Bittner

González

Walter

et al. 2003

Biopharm & Drug Disp

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In the current investigation, the alkaloid colchicine was administered intravenously to male Wistar rats both as a solution in isotonic sodium chloride (NaCl 0.9%, control group) and in NaCl 0.9%:Solutol HS 15 (95:5) at 1.5 mg/kg. At predetermined time points, plasma and urine were collected from the animals and analysed for colchicine and its demethylated metabolites by LC/MS-MS. In the presence of Solutol HS 15, colchicine clearance (CI) was significantly decreased and its maximum plasma concentration (c(max)) was significantly increased as compared to the control group (CI: 15.6+/-7.0 ml/min/kg vs 34.3+/-2.3 ml/min/kg; c(max) 3055.1+/-587.4 h vs 1260.1+/-223.7 h; p<0.05). Moreover, the amount of parent colchicine excreted into urine was markedly increased in the Solutol HS 15 treated group (41.50+/-3.23 vs 1.17+/-0.41% of total dose; p<0.05). By contrast, there was no statistically significant difference but a trend to lower values only in the volume of distribution (V(d) 13.3+/-2.2 l/h vs 31.4+/-17.7 l/h, p=0.35). The half-lives for the first (t(1/2 1stphase). 0.21+/-0.02 h vs 0.20+/-0.03 h) and second phase (t(1/2 2ndphase). 18.5+/-6.9 h vs 18.3+/-7.7 h) did not differ significantly in dependence on the dosing vehicle. The free fraction in rat plasma (FF), the blood/plasma (lambda) and erythrocyte/plasma concentration ratios (K(e)) were not significantly changed in the presence of different concentrations of Solutol HS 15 compared with surfactant-free incubations (overall means: 72.25+/-0.50% for FF, 0.80+/-0.02 for lambda, 0.46+/-0.04 for K(e)). In vitro, in rat hepatocytes, the clearance of colchicine was significantly reduced at 0.003% Solutol HS 15 present in the incubation medium (0.86+/-0.15 microl/min/10(-6) cells vs 1.46+/-0.06 microl/min/10(-6) cells). As colchicine exhibits a comparatively high aqueous solubility, an impact of Solutol HS 15 on the solubility of the alkaloid is very unlikely to be a reason for the observed effect. Therefore, our results indicate that the most likely reasons for the changed pharmacokinetic behaviour of colchicine in the presence of Solutol HS 15 are alterations of metabolism and/or transport as well as distribution and elimination processes.

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“…Colchicine is also released slowly from rat peritoneal mast cells, rat peritoneal macrophages, and human synovial cells [73][74][75][76] . Its primary excretory route in the human is the kidney, but the lung accounts for an unknown fraction of excreted drug [ 52,77 ] . The kinetics and metabolism of colchicine are shown in Table 9.4 .…”

Section: Pharmacokinetics Of Colchicinementioning

confidence: 99%

Management of Hyperuricemia and Gout

Newcombe¹

2012

Gout

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Biosynthesis and Isolation of Radioactive Colchicine

Cited by 25 publications

References 7 publications

Cytoskeletal myotoxicity from simvastatin and colchicine

Cytoskeletal myotoxicity from simvastatin and colchicine

Impact of solutol HS 15 on the pharmacokinetic behaviour of colchicine upon intravenous administration to male Wistar rats

Management of Hyperuricemia and Gout

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