title: The enterohepatic circulation of amanitin: kinetics and therapeutical implications.
abstract: BACKGROUND
  Amatoxin poisoning induces a delayed onset of acute liver failure which might be explained by the prolonged persistence of the toxin in the enterohepatic circulation. Aim of the study was to demonstrate amanitin kinetics in the enterohepatic circulation.
  
  
  METHODS
  Four pigs underwent α-amanitin intoxication receiving 0.35 mg/kg (n=2) or 0.15 mg/kg (n=2) intraportally. All pigs remained under general anesthesia throughout the observation period of 72 h. Laboratory values and amanitin concentration in systemic and portal plasma, bile and urine samples were measured.
  
  
  RESULTS
  Amanitin concentrations measured 5h after intoxication of 219±5ng/mL (0.35 mg/kg) and 64±3 (0.15 mg/kg) in systemic plasma and 201±8ng/mL, 80±13ng/mL in portal plasma declined to baseline levels within 24h. Bile concentrations simultaneously recorded showed 153±28ng/mL and 99±58ng/mL and decreased slightly delayed to baseline within 32 h. No difference between portal and systemic amanitin concentration was detected after 24h.
  
  
  CONCLUSIONS
  Amanitin disappeared almost completely from systemic and enterohepatic circulation within 24 h. Systemic detoxification and/or interrupting the enterohepatic circulation at a later date might be poorly effective.
authors.affiliation: Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Hoppe-Seyler-Strasse 3, Tuebingen 72076, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Thiel
authors.forename: Karolin
authors.initials: K
authors.lastname: Thiel
authors.forename: Wilfried
authors.initials: W
authors.lastname: Klingert
authors.forename: Andreas
authors.initials: A
authors.lastname: Diewold
authors.forename: Kathrin
authors.initials: K
authors.lastname: Scheuermann
authors.forename: Elmar
authors.initials: E
authors.lastname: Hawerkamp
authors.forename: Johannes
authors.initials: J
authors.lastname: Lauber
authors.forename: Johannes
authors.initials: J
authors.lastname: Scheppach
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Morgalla
authors.forename: Alfred
authors.initials: A
authors.lastname: Königsrainer
authors.forename: Martin
authors.initials: M
authors.lastname: Schenk
mesh_terms: D053959:Alpha-Amanitin / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000546:Amanitins / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004195:Disease Models, Animal; D004764:Enterohepatic Circulation; D005260:Female; D006651:Histocytochemistry; D017114:Liver Failure, Acute / Q000097:blood / Q000139:chemically induced / Q000378:metabolism* / Q000652:urine; D011517:Prothrombin Time; D013552:Swine
chemical_list: D053959:Alpha-Amanitin; D000546:Amanitins; C018207:amatoxin; D001219:Aspartate Aminotransferases