OBJECTIVE To determine pharmacokinetics and sedative effects of buprenorphine after IV and oral transmucosal (OTM) administration in guinea pigs.
ANIMALS 14 male guinea pigs (6 adults for preliminary experiment; eight 8 to 11-week-old animals for primary study).
PROCEDURES A preliminary experiment was conducted to determine an appropriate buprenorphine dose. In the primary study, buprenorphine (0.2 mg/kg) was administered IV or OTM, and blood samples were obtained. The pH of the oral cavity was measured before OTM administration. Sedation was scored for 6 hours on a scale of 0 to 3 (0 = no sedation and 3 = heavy sedation). After a 7-day washout period, procedures were repeated in a crossover manner. Plasma buprenorphine concentration was quantified, and data were analyzed with a noncompartmental pharmacokinetic approach.
RESULTS Mean peak plasma buprenorphine concentrations were 46.7 and 2.4 ng/mL after IV and OTM administration, respectively. Mean time to maximum plasma buprenorphine concentration was 1.5 and 71.2 minutes, and mean terminal half-life was 184.9 and 173.0 minutes for IV and OTM administration, respectively. There was a range of sedation effects (0 to 2) for both routes of administration, which resolved within the 6-hour time frame.
CONCLUSIONS AND CLINICAL RELEVANCE On the basis of pharmacokinetic parameters for this study, buprenorphine at 0.2 mg/kg may be administered IV every 7 hours or OTM every 4 hours to maintain a target plasma concentration of 1 ng/mL. Further studies are needed to evaluate administration of multiple doses and sedative effects in guinea pigs with signs of pain.
To evaluate the pharmacokinetics of hydromorphone hydrochloride after IM and IV administration to orange-winged Amazon parrots (Amazona amazonica).
8 orange-winged Amazon parrots (4 males and 4 females).
Hydromorphone (1 mg/kg) was administered once IM. Blood samples were collected 5 minutes and 0.5, 1.5, 2, 3, 6, and 9 hours after drug administration. Plasma hydromorphone concentrations were determined with liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were calculated with a compartmental model. The experiment was repeated 1 month later with the same dose of hydromorphone administered IV.
Plasma hydromorphone concentrations were > 1 ng/mL for 6 hours in 8 of 8 and 6 of 7 parrots after IM and IV injection, respectively. After IM administration, mean bioavailability was 97.6%, and mean maximum plasma concentration was 179.1 ng/mL 17 minutes after injection. Mean volume of distribution and plasma drug clearance were 4.24 L/kg and 64.2 mL/min/kg, respectively, after IV administration. Mean elimination half-lives were 1.74 and 1.45 hours after IM and IV administration, respectively.
CONCLUSIONS AND CLINICAL RELEVANCE
Hydromorphone hydrochloride had high bioavailability and rapid elimination after IM administration, with rapid plasma clearance and a large volume of distribution after IV administration in orange-winged Amazon parrots. Drug elimination half-lives were short. Further pharmacokinetic studies of hydromorphone and its metabolites, including investigation of multiple doses, different routes of administration, and sustained-release formulations, are recommended.
Objective—To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis).
Animals—9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex).
Procedures—Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from −5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were collected from −5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentrations of tramadol and its major metabolites were measured via high-performance liquid chromatography.
Results—Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administration of tramadol at a dose of 10 mg/kg were < 40 ng/mL for the entire time period, but oral administration at a dose of 30 mg/kg resulted in mean plasma concentrations > 100 ng/mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration.
Conclusions and Clinical Relevance—Oral administration of tramadol at a dose of 30 mg/kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analgesia in Hispaniolan Amazon parrots.
Objective—To compare serum concentrations of liposome-encapsulated butorphanol tartrate (LEBT) and standard butorphanol tartrate (STDBT) following SC and IM administration, respectively, and to evaluate analgesic effects of LEBT and STDBT after parenteral administration to Hispaniolan parrots.
Animals—11 adult Hispaniolan parrots.
Procedure—The ability of LEBT to prolong the duration of analgesia in an avian species was tested. Blood samples were collected at serial time points after SC administration of LEBT (10 mg/kg or 15 mg/kg) or IM administration of STDBT (5 mg/kg). Serum concentrations of butorphanol tartrate were determined by use of a commercial immunoassay that measured parent drug and metabolites. Analgesic efficacy was evaluated in parrots exposed to electrical and thermal stimuli. Foot withdrawal thresholds were recorded at baseline and at serial time points after LEBT (15 mg/kg), liposome vehicle, STDBT (2 mg/kg), or physiologic saline (0.9% NaCl) solution administration.
Results—LEBT had a prolonged in vivo release for up to 5 days. Negligible serum butorphanol and butorphanol metabolite concentrations were obtained at 24 hours after IM administration of STDBT. Analgesic efficacy of LEBT as measured by foot withdrawal threshold to noxious thermal and electrical stimuli persisted for 3 to 5 days following SC administration of LEBT.
Conclusions and Clinical Relevance—SC administration of LEBT provided analgesia and detectable serum butorphanol concentrations in Hispaniolan parrots for up to 5 days. The use of LEBT may allow for substantial improvement in long-term pain relief without subjecting birds to the stress of handling and multiple daily injections.
Objective—To evaluate the antinociceptive effects and duration of action of nalbuphine HCl administered IM on thermal thresholds in Hispaniolan Amazon parrots (Amazona ventralis).
Animals—14 healthy adult Hispaniolan Amazon parrots of unknown sex.
Procedures—3 doses of nalbuphine (12.5, 25, and 50 mg/kg, IM) and saline (0.9% NaCl) solution (control treatment) were evaluated in a blinded complete crossover experimental design by use of foot withdrawal threshold to a noxious thermal stimulus. Baseline data on thermal threshold were generated 1 hour before administration of nalbuphine or saline solution; thermal threshold measurements were obtained 0.5, 1.5, 3, and 6 hours after administration.
Results—Nalbuphine administered IM at 12.5 mg/kg significantly increased the thermal threshold (mean change, 2.4°C), compared with results for the control treatment, and significantly changed thermal threshold for up to 3 hours, compared with baseline results (mean change, 2.6° to 3.8°C). Higher doses of nalbuphine did not significantly change thermal thresholds, compared with results for the control treatment, but had a significant effect, compared with baseline results, for up to 3 and 1.5 hours after administration, respectively.
Conclusions and Clinical Relevance—Nalbuphine administered IM at 12.5 mg/kg significantly increased the foot withdrawal threshold to a thermal noxious stimulus in Hispaniolan Amazon parrots. Higher doses of nalbuphine did not result in significantly increased thermal thresholds or a longer duration of action and would be expected to result in less analgesic effect than lower doses. Further studies are needed to fully evaluate the analgesic effects of nalbuphine in psittacine species.
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.
Objective—To determine the pharmacokinetics of hydromorphone hydrochloride after IV and IM administration in American kestrels (Falco sparverius).
Animals—12 healthy adult American kestrels.
Procedures—A single dose of hydromorphone (0.6 mg/kg) was administered IM (pectoral muscles) and IV (right jugular vein); the time between IM and IV administration experiments was 1 month. Blood samples were collected at 5 minutes, 1 hour, and 3 hours (n = 4 birds); 0.25, 1.5, and 9 hours (4); and 0.5, 2, and 6 hours (4) after drug administration. Plasma hydromorphone concentrations were determined by means of liquid chromatography with mass spectrometry, and pharmacokinetic parameters were calculated with a noncompartmental model. Mean plasma hydromorphone concentration for each time was determined with naïve averaged pharmacokinetic analysis.
Results—Plasma hydromorphone concentrations were detectable in 2 and 3 birds at 6 hours after IM and IV administration, respectively, but not at 9 hours after administration. The fraction of the hydromorphone dose absorbed after IM administration was 0.75. The maximum observed plasma concentration was 112.1 ng/mL (5 minutes after administration). The terminal half-life was 1.25 and 1.26 hours after IV and IM administration, respectively.
Conclusion and Clinical Relevance—Results indicated hydromorphone hydrochloride had high bioavailability and rapid elimination after IM administration, with a short terminal half-life, rapid plasma clearance, and large volume of distribution in American kestrels. Further studies regarding the effects of other doses, other administration routes, constantrate infusions, and slow release formulations on the pharmacokinetics of hydromorphone hydrochloride and its metabolites in American kestrels may be indicated.
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 antinociceptive and sedative effects and duration of action of hydromorphone hydrochloride after IM administration to American kestrels (Falco sparverius).
Animals—11 healthy 2-year-old American kestrels.
Procedures—Hydromorphone (0.1, 0.3, and 0.6 mg/kg) and an equivalent volume of saline (0.9% NaCl) solution (control treatment) were administered IM to kestrels in a masked randomized complete crossover study design. Foot withdrawal response to a thermal stimulus was determined 30 to 60 minutes before (baseline) and 0.5, 1.5, 3, and 6 hours after treatment administration. Agitation-sedation scores were determined 3 to 5 minutes before each thermal test.
Results—Hydromorphone at 0.6 mg/kg, IM, significantly increased the thermal foot withdrawal threshold, compared with the response after administration of saline solution, for up to 3 hours, and hydromorphone at 0.1, 0.3, and 0.6 mg/kg, IM, significantly increased withdrawal responses for up to 6 hours, compared with baseline values. No significant differences in mean sedation-agitation scores were detected between hydromorphone and saline solution treatments; however, appreciable sedation was detected in 4 birds when administered 0.6 mg of hydromorphone/kg.
Conclusions and Clinical Relevance—Hydromorphone at the doses evaluated significantly increased the thermal nociception threshold for American kestrels for 3 to 6 hours. Additional studies with other types of stimulation, formulations, dosages, routes of administration, and testing times are needed to fully evaluate the analgesic and adverse effects of hydromorphone in kestrels and other avian species and the use of hydromorphone in clinical settings.