PHARMACOKINETICS AND PHARMACODYNAMICS OF ZOLPIDEM AFTER ORAL ADMINISTRATION OF A SINGLE DOSE IN DOGS

Objective: to determine whether this drug could be used for sedation and anti-anxiety effect in dogs. Animals: 8 male normal dogs. Procedure: Eight male adult dogs of different breeds were divided into two groups and given zolpidem orally at two different dose rates (group 1: 0.15 and group 2: 0.50 mg/kg), using an open, single-dose, two-strength, two-period, cross-over design. Drug plasma concentrations were evaluated using a validated HPLC-FL method, while pharmacodynamics were assessed using behavioural and clinical parameters. Results: The pharmacokinetics were dose-dependent, the plasma concentrations attained where lower than those for humans administered with the same doses. The low dose did not produce any clinical or adverse effect, while the high dose generated paradoxical CNS stimulation of approximately 1 h duration and a subsequent short and mild sedation phase. This sedation phase was not considered to be of clinical significance. The desired clinical effects were not produced at plasma levels less than or equal to 30 ng/mL which was on the cusp of the minimal plasma concentration producing side effects (60 ng/mL). Conclusions and Clinical Relevance: Zolpidem is not a suitable drug for inducing sedation in dogs.