title: Evaluation of plasma diazepam and nordiazepam concentrations following administration of diazepam intravenously or via suppository per rectum in dogs.
abstract: OBJECTIVE
  To evaluate the pharmacokinetics of diazepam administered per rectum via compounded (ie, not commercially available) suppositories and determine whether a dose of 2 mg/kg in this formulation would result in plasma concentrations shown to be effective for control of status epilepticus or cluster seizures (ie, 150 to 300 ng/mL) in dogs within a clinically useful interval (10 to 15 minutes).
  
  
  METHODS
  6 healthy mixed-breed dogs.
  
  
  METHODS
  Dogs were randomly assigned to 2 groups of 3 dogs each in a crossover-design study. Diazepam (2 mg/kg) was administered IV or via suppository per rectum, and blood samples were collected at predetermined time points. Following a 6- or 7-day washout period, each group received the alternate treatment. Plasma concentrations of diazepam and nordiazepam were analyzed via reversed phase high-performance liquid chromatography.
  
  
  RESULTS
  Plasma concentrations of diazepam and nordiazepam exceeded the targeted range ≤ 3 minutes after IV administration in all dogs. After suppository administration, targeted concentrations of diazepam were not detected in any dogs, and targeted concentrations of nordiazepam were detected after 90 minutes (n = 2 dogs) or 120 minutes (3) or were not achieved (1).
  
  
  CONCLUSIONS
  On the basis of these results, administration of 2 mg of diazepam/kg via the compounded suppositories used in the present study cannot be recommended for emergency treatment of seizures in dogs.
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA. probst@cvm.msu.edu
authors.forename: Curtis W
authors.initials: CW
authors.lastname: Probst
authors.forename: William B
authors.initials: WB
authors.lastname: Thomas
authors.forename: Tamberlyn D
authors.initials: TD
authors.lastname: Moyers
authors.forename: Tomas
authors.initials: T
authors.lastname: Martin
authors.forename: Sherry
authors.initials: S
authors.lastname: Cox
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D019540:Area Under Curve; D018592:Cross-Over Studies; D003975:Diazepam / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D004285:Dogs / Q000097:blood*; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D003708:Nordazepam / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D013488:Suppositories
chemical_list: D000927:Anticonvulsants; D013488:Suppositories; D003708:Nordazepam; D003975:Diazepam