Fab fragments of ovine antibody to colchicine enhance its clearance in the rat.
Clin Toxicol (Phila)
; 53(5): 427-32, 2015 Jun.
Article
em En
| MEDLINE
| ID: mdl-25858137
ABSTRACT
CONTEXT Colchicine is an anti-inflammatory alkaloid used for the treatment of acute gout, but has a narrow therapeutic index. Colchicine overdoses are relatively rare, but have high mortality requiring rapid treatment. OBJECTIVE:
To evaluate the ability of a newly available ovine fragment antigen-binding (Fab) antibody to colchicine (ColchiFab(™)) to protect rats against renal and other injury 24 h after colchicine ingestion. MATERIALS ANDMETHODS:
Rats were gavaged with colchicine (5 mg/kg), then 2 h later injected intraperitoneally with 5 ml of sterile saline, or Fab anti-colchicine, a newly available ovine antibody to colchicine. Samples of blood were taken at 1, 2, 5 and 24 h after gavage, and urine was collected from 5 to 24 h after gavage. Concentrations of colchicine in tissue, blood and urine were measured by liquid chromatography/mass spectrometry, concentrations of Fab anti-colchicine, urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 or KIM-1 by enzyme-linked immunosorbent assay or ELISA, while concentrations of creatine kinase and creatinine (Cr) were measured enzymatically.RESULTS:
Colchicine equilibrated rapidly throughout the body and increased serum creatine kinase. Fab anti-colchicine also rapidly redistributed to the blood and remained at high concentrations over 24 h. Fab anti-colchicine caused a rapid 7.1-fold increase in serum colchicine level, followed by excretion of both colchicine and Fab anti-colchicine through the urine. This was associated with the accumulation of colchicine in the kidney, a reversal of colchicine-induced diarrhoea, and increasing urinary NGAL level; from 168 ± 48 to 477 ± 255 ng/mmol Cr [mean ± standard deviation or SD].DISCUSSION:
Fab anti-colchicine greatly increased the clearance of colchicine, although increasing NGAL level suggested the presence of mild kidney damage.CONCLUSION:
These data suggest clinical utility for Fab anti-colchicine in the treatment of colchicine overdose.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Intoxicação
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Fragmentos Fab das Imunoglobulinas
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Colchicina
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Anti-Inflamatórios
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Antídotos
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article