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.
Animals—8 clinically normal sexually intact male dogs of various breeds.
Procedures—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 and Clinical Relevance—Results indicated that zolpidem is not a suitable drug for inducing sedation in dogs.
To evaluate the pharmacokinetics of acetaminophen (APAP) after single-dose IV and PO in the goose; to quantify APAP and its main metabolites in goose muscle, heart, lung, liver, and kidney; and to perform a histopathologic evaluation of goose stomach, duodenum, liver, and kidney tissues for potential signs of toxicity.
Geese were randomly divided into 3 groups (n = 8). Group I received APAP (10 mg/kg) IV, and groups II and III received the same dose PO. Groups I and II were used for the pharmacokinetic assessment, and group III was used for the residue analysis and histopathologic evaluation. APAP and its metabolites were quantified in plasma and tissues by ultra–high-performance liquid chromatography–tandem mass spectrometry, and the pharmacokinetic analysis was performed using a noncompartmental approach.
APAP plasma concentrations were lower than those of the metabolites in similar selected time points after both treatments. After IV treatment, the APAP area under the curve value was statistically higher than that after PO administration, resulting in an oral bioavailability of 46%. In contrast, the area under the curve of the metabolites following PO administration was statistically higher than those found after IV administration. Tissue residues of APAP were highest in the liver, with an accumulation index > 1. Fatty degeneration of hepatocytes was observed 24 hours after administration of APAP.
In geese, treatment by PO administration of APAP shows incomplete absorption and a slight accumulation in lung and liver. Tissue alterations occurred in the liver at 24 hours, while no signs of toxicity were found in the other tested organs.