Toxicokinetics of alpha amanitin in rats

TOXİCOKİNETİCS OF THE ALPHA AMANİTİN İN RATSAmanita phalloides is the species which cause more than % 95 lethal mushrooms? poisoning. There have been determined two groups of toxin in these mushrooms. These toxins are known as amanitin group and phalloidin group. Among toxins, the most frequent toxin is ?-amanitin type toxin and there are a lot of distributions in the mushroom. ?-amanitin is specific inhibitor of RNA polymerase II. Toxicokinetics of this toxin is very important about poisoning caused mushrooms but pharmacokinetics of this toxin has not been sufficiently determined.In recent field study at October-December in 2010, Amanita phalloides was adequately collected in forest around the Düzce. Toxins in the mushrooms were analyzed with HPLC method. In our study, ?-amanitin (1 mg/kg) was administrated via oral and intravenously in rats at different times ((2.-5.-10.-15.-20.-45.-60.-90. minutes and 2.-3.-4.5.-6.-9.-12.-24 hours) under anaesthesia. After that, we will give ?-amanitin to rats. In the different times, blood specimens of the taking from rats will be analyzed for ?-amanitin by using HPLC methods (C18 column, amonium asetate: acetonitrile: methanol (80:10:10,v/v/v) mobile phase, and 1 mL/min. isoacratic flows).Results from analyzes that we were done, toxicokinetics of ?-amanitin is demonstrate compliance with ?two compartment-open model?, oral bioavailability F = 0.936, tmax: 2-3 hours (2.64), Cmax-oral = 2.86 ± 0.08 µg/ml, Cmax-i.v. = 12.01 ± 0.07 µg/ml, clearance CL = 75.91 ± 9.11 ml/h/kg, elimination half life (t1/2ß) 110.4 ± 0.30 min.We explain parameters of toxicokinetics of ?-amanitin which oral bioavailability, elimination half life, tmax, Cmax, clearance and earned to literatures in rats. Furthermore there will be also to take advantages of this data at mushrooms poisoning cases.Keywords: Amanita phalloides, ?-amanitin, HPLC, toxicokinetics, bioavailability, clearance