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Submitted to: Toxicon
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 5/3/2017 Publication Date: 5/4/2017 Citation: Welch, K.D., Gardner, D.R., Stonecipher, C.A., Green, B.T., Pfister, J.A. 2017. Serum toxicokinetics after intravenous and oral dosing of larkspur toxins in goats. Toxicon. 133:91-94. doi: 10.1016/j.toxicon.2017.05.008. Interpretive Summary: There are over 60 species of larkspur plants (Delphinium spp.) in western North America. Larkspurs are acutely toxic to cattle, causing a significant number of cattle death losses every year. The toxicity of all larkspurs is due to norditerpenoid alkaloids including the alkaloids methyllycaconitine (MLA) and deltaline. Previous studies have characterized the serum toxicokinetics of MLA and deltaline in cattle after oral dosing with several species of tall larkspurs. However, those studies were all performed by orally dosing plant material. Consequently some toxicokinetic parameters could not be definitively determined. In this study, we compared the serum toxicokinetic profile of the larkspur alkaloids MLA and deltaline in goats dosed both IV and via oral gavage. The results from this study indicate that the toxic alkaloids in larkspurs undergo flip-flop kinetics, meaning the rate of absorption of the alkaloids is slower than the rate of elimination. The implications of flip-flop kinetics are that the absorption of the alkaloids is the rate limiting factor for larkspur toxins and therefore the mean residence time for the toxins are increased. Thus, in the case of animals poisoned by larkspurs, the slow absorption of the toxic alkaloids results in a wider toxic window. Additionally, treated animals may relapse due to the continued absorption of the toxic alkaloids. Consequently, for severely poisoned animals an effective treatment may need to include inhibition of absorption of the larkspur alkaloids by some manner, such as, activated charcoal administration. Technical Abstract: Poisoning of cattle by larkspur plants (Delphinium spp.) is a concern for cattle ranchers in western North America. Previous research studies have evaluated the toxicokinetic profile of multiple larkspur toxins in several livestock species. However, those studies were all performed by orally dosing plant material. Consequently some toxicokinetic parameters could not be definitively determined. In this study, we compared the serum toxicokinetic profile of the larkspur alkaloids methyllycaconitine (MLA) and deltaline in goats dosed both IV and via oral gavage. The results from this study indicate that the toxic alkaloids in larkspurs undergo flip-flop kinetics, meaning the rate of absorption of the alkaloids is slower than the rate of elimination. The implications of flip-flop kinetics in treating animals poisoned by larkspur is discussed. |
