title: Fab fragments of ovine antibody to colchicine enhance its clearance in the rat.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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].
  
  
  CONCLUSIONS
  Fab anti-colchicine greatly increased the clearance of colchicine, although increasing NGAL level suggested the presence of mild kidney damage.
  
  
  CONCLUSIONS
  These data suggest clinical utility for Fab anti-colchicine in the treatment of colchicine overdose.
authors: Department of Nephrology, Prince of Wales Hospital , Sydney , Australia.
authors: Philip W
authors: PW
authors: Peake
authors: Timothy J
authors: TJ
authors: Pianta
authors: Lena
authors: L
authors: Succar
authors: Mangalee
authors: M
authors: Fernando
authors: Nicholas A
authors: NA
authors: Buckley
authors: Zoltan H
authors: ZH
authors: Endre
mesh_terms: D000209:Acute-Phase Proteins / Q000652:urine; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics / Q000633:toxicity* / Q000652:urine; D000931:Antidotes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015815:Cell Adhesion Molecules / Q000652:urine; D003078:Colchicine / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics / Q000633:toxicity* / Q000652:urine; D003402:Creatine Kinase / Q000097:blood; D003967:Diarrhea / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D011041:Poisoning / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D011518:Proto-Oncogene Proteins / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D065667:Renal Elimination / Q000187:drug effects; D012756:Sheep; D014018:Tissue Distribution
chemical_list: D000209:Acute-Phase Proteins; D000893:Anti-Inflammatory Agents; D000931:Antidotes; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D003078:Colchicine; D003402:Creatine Kinase; D007140:Immunoglobulin Fab Fragments; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; C110936:Havcr1 protein, rat; C097278:Lcn2 protein, rat
keywords: ColchiFab; Colchicine; Fab antibody; Kidney; NGAL; Urine