Distribution of deoxynivalenol in cerebral spinal fluid following administration to swine and sheep.
Deoxynivalenol (DON) is one of the major mycotoxins produced by Fusarium fungi. In evaluating DON as a potent CNS (emetic, anorexic) agent, its cerebral spinal fluid (CSF) and plasma pharmacokinetics were studied in pigs, a species very sensitive to the effects of DON, and sheep, a more tolerant animal. After intravenous administration, DON was detected very rapidly (less than 2.5 min) in the CSF of both species, but whereas peak levels (t-max) occurred at 5-10 min in sheep, in swine it was 30-60 min. It would appear that the very rapid and extensive tissue distribution of DON in swine (Vd gamma = 1.13 1 kg-1) may be slowing the rate of diffusion of the toxin into the CSF compared to sheep (Vd beta = 0.19 1 kg-1) where the toxin is confined essentially to the extracellular compartment. Area under curve calculations indicate approximately 2 1/2 times the amount of toxin eventually reaches the pig CSF compared to sheep CSF. A good relationship between blood-CSF DON levels was apparent in both species, although limitations in detection methods made it impossible to resolve a slow terminal phase (gamma) in swine CSF which was evident in the plasma profile after iv administration. Following oral administration of DON to pigs, a close correlation between plasma and CSF DON levels was observed. The toxin could be detected in CSF for up to 20 hr post-dosing.
Prelusky
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Animal Research Centre, Agriculture Canada Ottawa, Ontario.
Hartin
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Trenholm
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D000284:Administration, Oral; D000818:Animals; D006207:Half-Life; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D012717:Sesquiterpenes / Q000134:cerebrospinal fluid*; D012756:Sheep / Q000134:cerebrospinal fluid* / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D013552:Swine / Q000134:cerebrospinal fluid* / Q000378:metabolism; D014255:Trichothecenes / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics
D012717:Sesquiterpenes; D014255:Trichothecenes; C007262:deoxynivalenol