Pharmacokinetics and protein binding of trichothecene mycotoxins, T-2 toxin and HT-2 toxin, in dogs.
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 and 73 +/- 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.
Sintov
A
A
Department of Pharmacy, School of Pharmacy, Hebrew University of Jerusalem, Israel.
Bialer
M
M
Yagen
B
B
D000818:Animals; D001711:Biotransformation; D004285:Dogs; D005260:Female; D006207:Half-Life; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D011485:Protein Binding; D012717:Sesquiterpenes / Q000493:pharmacokinetics*; D013605:T-2 Toxin / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*
D012717:Sesquiterpenes; D013605:T-2 Toxin; C012351:HT-2 toxin