The enterohepatic circulation of amanitin: Kinetics and therapeutical implications

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 a-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 +/- 5 ng/mL (0.35 mg/kg) and 64 +/- 3 (0.15 mg/kg) in systemic plasma and 201 +/- 8 ng/mL, 80 +/- 13 ng/mL in portal plasma declined to baseline levels within 24 h. Bile concentrations simultaneously recorded showed 153 +/- 28 ng/mL and 99 +/- 58 ng/mL and decreased slightly delayed to baseline within 32 h. No difference between portal and systemic amanitin concentration was detected after 24 h. Conclusions: Amanitin disappeared almost completely from systemic and enterohepatic circulation within 24h. Systemic detoxification and/or interrupting the enterohepatic circulation at a later date might be poorly effective. (C) 2011 Elsevier Ireland Ltd. All rights reserved.