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Toxicokinetics of norditerpenoid alkaloids from low larkspur (Delphinium andersonii) orally administered to cattle

Author:
Green, Benedict T., Welch, Kevin D., Gardner, Dale R., Stegelmeier, Bryan L., Pfister, James A., Cook, Daniel, Panter, Kip E.
Source:
American journal of veterinary research 2012 v.73 no.8 pp. 1318-1324
ISSN:
0002-9645
Subject:
Angus, Delphinium bicolor, beef cattle, blood serum, crates, diterpenoid alkaloids, half life, heart rate, lethal dose 50, mice, oral administration, pharmacokinetics, poisoning, steers
Abstract:
Objective: To determine the toxicokinetics of N-(methylsuccinimido)anthranoyllycoctonine–type low larkspur alkaloids in beef cattle. Animals: 5 Black Angus steers and 35 Swiss Webster mice. Procedures: Low larkspur (Delphinium andersonii) was collected, dried, ground, and administered to 5 steers via oral gavage to provide a dose of 12 mg of N-(methylsuccinimido)-anthranoyllycoctonine alkaloids/kg. Steers were housed in metabolism crates for 96 hours following larkspur administration; heart rate was monitored continuously, and blood samples were collected periodically for analysis of serum concentrations of 16-deacetylgeyerline, methyllycaconitine, geyerline, and nudicauline and assessment of kinetic parameters. The LD50 of a total alkaloid extract from D andersonii was determined in Swiss Webster mice. Results: The alkaloids were quickly absorbed, with a maximum serum concentration achieved within 18 hours after administration. Geyerline and nudicauline coeluted as 1 peak and were considered together for toxicokinetic analysis. Mean ± SD elimination half-life was 18.4 ± 4.4 hours, 15.6 ± 1.5 hours, and 16.5 ± 5.1 hours for 16-deacetylgeyerline, methyllycaconitine, and geyerline and nudicauline, respectively. There were significant differences in maximum serum concentration, amount absorbed, and distribution half-life among the 4 alkaloids. The mouse LD50 was 9.8 mg/kg. Conclusions and Clinical Relevance: Results suggested that clinical poisoning was likely to be most severe approximately 18 hours after exposure. Cattle should be closely monitored for at least 36 hours after initial exposure. Additionally, a withdrawal time of approximately 7 days would be required to clear > 99% of the toxic alkaloids from the serum of cattle that have ingested low larkspur.
Agid:
319328