title: Pharmacokinetics and pharmacodynamics of zolpidem after oral administration of a single dose in dogs.
abstract: OBJECTIVE
  To evaluate the pharmacokinetics and pharmacodynamics of zolpidem after oral administration of a single dose (0.15 or 0.50 mg/kg) and assess any associated antianxiety and sedative effects in dogs.
  
  
  METHODS
  8 clinically normal sexually intact male dogs of various breeds.
  
  
  METHODS
  Dogs were assigned to 2 groups (4 dogs/group) and administered zolpidem orally once at a dose of 0.15 or 0.50 mg/kg in a crossover study; each dog received the other treatment once after an interval of 1 week. Blood samples were collected before and at intervals during the 24-hour period following dose administration. For each time point, plasma zolpidem concentration was evaluated via a validated method of high-performance liquid chromatography coupled with fluorescence detection, and pharmacodynamics were assessed via subjective assessments of sedation and level of agitation and selected clinical variables.
  
  
  RESULTS
  The pharmacokinetic profile of zolpidem in dogs was dose dependent, and the plasma drug concentrations attained were lower than those for humans administered equivalent doses. The lower dose did not result in any clinical or adverse effects, but the higher dose generated paradoxical CNS stimulation of approximately 1 hour's duration and a subsequent short phase of mild sedation. This sedation phase was not considered to be of clinical relevance. The desired clinical effects were not evident at plasma zolpidem concentrations ≤ 30 ng/mL, and the minimal plasma concentration that induced adverse effects was 60 ng/mL.
  
  
  CONCLUSIONS
  Results indicated that zolpidem is not a suitable drug for inducing sedation in dogs.
authors.affiliation: Department of Veterinary Clinics, Veterinary Teaching Hospital, University of Pisa, San Piero a Grado, 56122 Pisa, Italy. mgiorgi@vet.unipi.it
authors.forename: Mario
authors.initials: M
authors.lastname: Giorgi
authors.forename: Diego Angel
authors.initials: DA
authors.lastname: Portela
authors.forename: Gloria
authors.initials: G
authors.lastname: Breghi
authors.forename: Angela
authors.initials: A
authors.lastname: Briganti
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D018592:Cross-Over Studies; D004285:Dogs / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D058785:GABA-A Receptor Agonists / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D011725:Pyridines / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D000077334:Zolpidem
chemical_list: D058785:GABA-A Receptor Agonists; D006993:Hypnotics and Sedatives; D011725:Pyridines; D000077334:Zolpidem