Pharmacokinetics and protein binding of trichothecene mycotoxins, T-2 toxin and HT-2 toxin, in dogs

A. Sintov, M. Bialer and B. Yagen. Pharmacokinetics and protein binding of trichothecene mycotoxins, T-2 toxin and HT-2 toxin, in dogs. Toxicon 26, 153 - 160, 1988. - The pharmacokinetics of T-2 toxin, following i.m. and i.v. administration (0.4 mg/kg), were investigated in five dogs. Following i.m. administration, the mean pharmacokinetic parameters for T-2 and HT-2 toxins were, respectively: apparent half-life 21 ± 5 and73 ± 7 min; peak plasma concentration 182 ± 42 and 74 ± 16 ng/ml; time to reach peak plasma concentration 9.4 ± 6.4 and 49 ± 11 min. Mean residence time calculation, using moment analysis, showed that the terminal slope of T-2 toxin plasma levels following i.m. administration corresponds to the absorption rate constant of the toxin due to the flip-flop phenomenon. T-2 toxin was completely absorbed following i.m. administration and its absolute bioavailability was 1.17 ± 0.25. A plasma protein binding study showed that in a concentration range of 70 - 500 ng/ml, T-2 and HT-2 toxins have a mean free fraction of 30.6 ± 3.1% and 32.6 ± 3.6% with no concentration dependency. At physiological conditions (temperature and pH), both T-2 and HT-2 toxins were unstable in whole blood and their in vitro stability half-lives were 6.9 and 0.84 hr, respectively. However, under similar conditions, these toxins were stable in plasma for 7 hr. Their instability in whole blood, therefore, may be related to enzymes present in the blood cells.