Sedatives have been used for a long time as animal tranquillisers to prevent stress and weight loss during their transportation. The proper determination of these substances in food of animal origin is essential for consumer safety.

OBJECTIVE To determine the pharmacokinetics and sedative effects of 2 doses of a concentrated buprenorphine formulation after SC administration to red-tailed hawks (Buteo jamaicensis). ANIMALS 6 adult red-tailed hawks. PROCEDURES Concentrated buprenorphine (0.3 mg/kg, SC) was administered to all birds. Blood samples were collected at 10 time points over 24 hours after drug administration to determine plasma buprenorphine concentrations. After a 4-week washout period, the same birds received the same formulation at a higher dose (1.8 mg/kg, SC), and blood samples were collected at 13 time points over 96 hours. Hawks were monitored for adverse effects and assigned agitation-sedation scores at each sample collection time. Plasma buprenorphine concentrations were quantified by liquid chromatography–tandem mass spectrometry. RESULTS Mean time to maximum plasma buprenorphine concentration was 7.2 minutes and 26.1 minutes after administration of the 0.3-mg/kg and 1.8-mg/kg doses, respectively. Plasma buprenorphine concentrations were > 1 ng/mL for mean durations of 24 and 48 hours after low- and high-dose administration, respectively. Mean elimination half-life was 6.23 hours for the low dose and 7.84 hours for the high dose. Mean agitation-sedation scores were higher (indicating some degree of sedation) than the baseline values for 24 hours at both doses. No clinically important adverse effects were observed. CONCLUSIONS AND CLINICAL RELEVANCE Concentrated buprenorphine was rapidly absorbed, and plasma drug concentrations considered to have analgesic effects in other raptor species were maintained for extended periods. Most birds had mild to moderate sedation. Additional studies are needed to evaluate the pharmacodynamics of these doses of concentrated buprenorphine in red-tailed hawks.

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.

The effects of 2 different continuous rate infusions (CRIs) of medetomidine over an 8-hour period on sedation score, selected cardiopulmonary parameters, and serum levels of medetomidine were evaluated in 6 healthy, conscious dogs using a crossover study design. The treatment groups were: CONTROL = saline bolus followed by saline CRI; MED1 = 2 μg/kg body weight (BW) medetomidine loading dose followed by 1 μg/kg BW per hour CRI; and MED2 = 4 μg/kg BW medetomidine loading dose followed by 2 μg/kg BW per hour CRI. Sedation score (SS), heart rate (HR), respiratory rate (RR), temperature (TEMP), systolic arterial pressure (SAP), mean arterial pressure (MAP), and diastolic arterial pressure (DAP), arterial and mixed venous blood gas analyses, lactate, and plasma levels of medetomidine were evaluated at baseline, at various intervals during the infusion, and 2 h after terminating the infusion. Statistical analysis involved a repeated measures linear model. Both infusion rates of medetomidine-induced dose-dependent increases in SS and dose-dependent decreases in HR, SAP, MAP, and DAP were measured. Respiratory rate (RR), TEMP, central venous pH, central venous oxygen tension, and oxygen extraction ratio also decreased significantly in the MED2 group at certain time points. Arterial oxygen and carbon dioxide tensions were not significantly affected by either infusion rate. In healthy dogs, both infusion rates of medetomidine-induced clinically relevant sedative effects, accompanied by typical alpha2 agonist-induced hemodynamic effects, which plateaued during the infusion and subsequently returned to baseline. While additional studies in unhealthy animals are required, the results presented here suggest that medetomidine infusions at the doses studied may be useful in canine patients requiring sedation for extended periods.

OBJECTIVE To determine the pharmacokinetics of hydromorphone hydrochloride after IV and IM administration in guinea pigs (Cavia porcellus). ANIMALS 8 healthy adult guinea pigs (4 sexually intact females and 4 sexually intact males). PROCEDURES In a crossover study, hydromorphone (0.3 mg/kg) was administered once IM (epaxial musculature) or IV (cephalic catheter) to each guinea pig at a 1-week interval (2 treatments/guinea pig). Blood samples were collected before and at predetermined intervals after drug administration via a vascular access port. Plasma hydromorphone concentrations were determined by liquid chromatography–tandem mass spectrometry. Noncompartmental analysis of data was used to calculate pharmacokinetic parameters. RESULTS Mean ± SD clearance and volume of distribution for hydromorphone administered IV were 52.8 ± 13.5 mL/min/kg and 2.39 ± 0.479 L/kg, respectively. Mean residence time determined for the IV and IM administration routes was 0.77 ± 0.14 hours and 0.99 ± 0.34 hours, respectively. The maximum observed plasma concentration following IM administration of hydromorphone was 171.9 ± 29.4 ng/mL. No sedative effects were observed after drug administration by either route. CONCLUSIONS AND CLINICAL RELEVANCE Pharmacokinetic data indicated that hydromorphone at a dose of 0.3 mg/kg may be administered IV every 2 to 3 hours or IM every 4 to 5 hours to maintain a target plasma concentration between 2 and 4 ng/mL in guinea pigs. Hydromorphone had high bioavailability after IM administration. Further research is necessary to evaluate the effects of other doses and administration routes and the analgesic effects of hydromorphone in guinea pigs.

OBJECTIVE To evaluate the thermal antinociceptive effects and pharmacokinetics of hydromorphone hydrochloride after IM administration to cockatiels (Nymphicus hollandicus). ANIMALS 16 healthy adult cockatiels. PROCEDURES During the first of 2 study phases, each cockatiel received each of 4 treatments (hydromorphone at doses of 0.1, 0.3, and 0.6 mg/kg and saline [0.9% NaCl] solution [0.33 mL/kg; control], IM), with a 14-day interval between treatments. For each bird, foot withdrawal to a thermal stimulus was determined following assignment of an agitation-sedation score at predetermined times before and for 6 hours after each treatment. During the second phase, a subset of 12 birds received hydromorphone (0.6 mg/kg, IM), and blood samples were collected at predetermined times for 9 hours after drug administration. Plasma hydromorphone concentration was determined by liquid chromatography–mass spectrometry. Noncompartmental analysis of sparse data was used to calculate pharmacokinetic parameters. RESULTS Thermal withdrawal response did not differ among the 4 treatment groups at any time. Agitation-sedation scores following administration of the 0.3-and 0.6-mg/kg doses of hydromorphone differed significantly from those treated with saline solution and suggested the drug had a sedative effect. Plasma hydromorphone concentrations were > 1 ng/mL for 3 to 6 hours after drug administration in all birds. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that IM administration of hydromorphone at the evaluated doses did not increase the thermal withdrawal threshold of cockatiels despite plasma drug concentrations considered therapeutic for other species. Further research is necessary to evaluate the analgesic effects of hydromorphone in cockatiels.

OBJECTIVE To determine the pharmacokinetic and pharmacodynamic effects of midazolam following IV and IM administration in sheep. ANIMALS 8 healthy adult rams. PROCEDURES Sheep were administered midazolam (0.5 mg/kg) by the IV route and then by the IM route 7 days later in a crossover study. Physiologic and behavioral variables were assessed and blood samples collected for determination of plasma midazolam and 1-hydroxymidazolam (primary midazolam metabolite) concentrations immediately before (baseline) and at predetermined times for 1,440 minutes after midazolam administration. Pharmacokinetic parameters were calculated by compartmental and noncompartmental methods. RESULTS Following IV administration, midazolam was rapidly and extensively distributed and rapidly eliminated; mean ± SD apparent volume of distribution, elimination half-life, clearance, and area under the concentration-time curve were 838 ± 330 mL/kg, 0.79 ± 0.44 hours, 1,272 ± 310 mL/h/kg, and 423 ± 143 h·ng/mL, respectively. Following IM administration, midazolam was rapidly absorbed and bioavailability was high; mean ± SD maximum plasma concentration, time to maximum plasma concentration, area under the concentration-time curve, and bioavailability were 820 ± 268 ng/mL, 0.46 ± 0.26 hours, 1,396 ± 463 h·ng/mL, and 352 ± 148%, respectively. Respiratory rate was transiently decreased from baseline for 15 minutes after IV administration. Times to peak sedation and ataxia after IV administration were less than those after IM administration. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated midazolam was a suitable short-duration sedative for sheep, and IM administration may be a viable alternative when IV administration is not possible.

Objective—To evaluate the thermal antinociceptive effects and duration of action of buprenorphine hydrochloride after IM administration to American kestrels (Falco sparverius). Animals—12 healthy 3-year-old American kestrels. Procedures—Buprenorphine hydrochloride (0.1, 0.3, and 0.6 mg/kg) and a control treatment (saline [0.9% NaCl] solution) were administered IM in a randomized crossover experimental design. Foot withdrawal response to a thermal stimulus was determined 1 hour before (baseline) and 1.5, 3, and 6 hours after treatment administration. Agitation-sedation scores were determined 3 to 5 minutes before each thermal stimulus. Adverse effects were monitored for 6 hours after treatment administration. Results—Buprenorphine hydrochloride at 0.1, 0.3, and 0.6 mg/kg, IM, increased thermal threshold for 6 hours, compared with the response for the control treatment. There were no significant differences among buprenorphine treatments. A mild sedative effect was detected at a dose of 0.6 mg of buprenorphine/kg. Conclusion and Clinical Relevance—At the doses tested, buprenorphine hydrochloride resulted in thermal antinociception in American kestrels for at least 6 hours, which suggested that buprenorphine has analgesic effects in this species. Further studies with longer evaluation periods and additional forms of noxious stimuli, formulations, dosages, and routes of administration are needed to fully evaluate the analgesic effects of buprenorphine in American kestrels.

Objective: To determine the antinociceptive and sedative effects of tramadol in Hispaniolan Amazon parrots (Amazona ventralis) following IV administration. Animals: 11 healthy Hispaniolan Amazon parrots of unknown sex. Procedures: Tramadol hydrochloride (5 mg/kg, IV) and an equivalent volume (≤ 0.34 mL) of saline (0.9% NaCl) solution were administered to parrots in a complete crossover study design. Foot withdrawal response to a thermal stimulus was determined 30 to 60 minutes before (baseline) and 15, 30, 60, 120, and 240 minutes after treatment administration; agitation-sedation scores were determined for parrots at each of those times. Results: The estimated mean changes in temperature from the baseline value that elicited a foot withdrawal response were 1.65° and −1.08°C after administration of tramadol and saline solution, respectively. Temperatures at which a foot withdrawal response was elicited were significantly higher than baseline values at all 5 evaluation times after administration of tramadol and were significantly lower than baseline values at 30, 120, and 240 minutes after administration of saline solution. No sedation, agitation, or other adverse effects were observed in any of the parrots after administration of tramadol. Conclusions and Clinical Relevance: Tramadol hydrochloride (5 mg/kg, IV) significantly increased the thermal nociception threshold for Hispaniolan Amazon parrots in the present study. Sedation and adverse effects were not observed. These results are consistent with results of other studies in which the antinociceptive effects of tramadol after oral administration to parrots were determined.

Objective-To evaluate the thermal antinociceptive and sedative effects and duration of action of tramadol hydrochloride after oral administration to American kestrels (Falco sparverius). Animals-12 healthy 3-year-old American kestrels. Procedures-Tramadol (5, 15, and 30 mg/kg) and a control suspension were administered orally in a masked randomized crossover experimental design. Foot withdrawal response to a thermal stimulus was determined 1 hour before (baseline) and 0.5, 1.5, 3, 6, and 9 hours after treatment. Agitation-sedation scores were determined 3 to 5 minutes before each thermal stimulus test. Results-The lowest dose of tramadol evaluated (5 mg/kg) significantly increased the thermal foot withdrawal thresholds for up to 1.5 hours after administration, compared with control treatment values, and for up to 9 hours after administration, compared with baseline values. Tramadol at doses of 15 and 30 mg/kg significantly increased thermal thresholds at 0.5 hours after administration, compared with control treatment values, and up to 3 hours after administration, compared with baseline values. No significant differences in agitation-sedation scores were detected between tramadol and control treatments. Conclusions and Clinical Relevance-Results indicated oral administration of 5 mg of tramadol/kg significantly increased thermal nociception thresholds for kestrels for 1.5 hours, compared with a control treatment, and 9 hours, compared with baseline values; higher doses resulted in less pronounced antinociceptive effects. Additional studies with other types of stimulation, formulations, dosages, routes of administration, and testing times would be needed to fully evaluate the analgesic and adverse effects of tramadol in kestrels and other avian species.