title: Toxicokinetics of norditerpenoid alkaloids from low larkspur (Delphinium andersonii) orally administered to cattle.
abstract: OBJECTIVE
  To determine the toxicokinetics of N-(methylsuccinimido)anthranoyllycoctonine-type low larkspur alkaloids in beef cattle.
  
  
  METHODS
  5 Black Angus steers and 35 Swiss Webster mice.
  
  
  METHODS
  -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 LD(50) 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 LD(50) was 9.8 mg/kg.
  
  
  CONCLUSIONS
  -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.
authors: Poisonous Plant Research Laboratory, Agricultural Research Service, USDA, Logan, UT 84321, USA. Ben.Green@ars.usda.gov
authors: Benedict T
authors: BT
authors: Green
authors: Kevin D
authors: KD
authors: Welch
authors: Dale R
authors: DR
authors: Gardner
authors: Bryan L
authors: BL
authors: Stegelmeier
authors: James A
authors: JA
authors: Pfister
authors: Daniel
authors: D
authors: Cook
authors: Kip E
authors: KE
authors: Panter
mesh_terms: D000284:Administration, Oral; D000470:Alkaloids / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D000821:Animal Feed / Q000633:toxicity*; D000818:Animals; D019540:Area Under Curve; D002417:Cattle / Q000378:metabolism*; D031882:Delphinium / Q000378:metabolism* / Q000633:toxicity*; D004224:Diterpenes / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity; D006207:Half-Life; D007928:Lethal Dose 50; D008297:Male; D051379:Mice
chemical_list: D000470:Alkaloids; D004224:Diterpenes