OBJECTIVE To determine pharmacokinetics after IM and oral administration of a single dose of meloxicam to American flamingos (Phoenicopertus ruber). ANIMALS 14 adult flamingos. PROCEDURES Flamingos were allocated to 2 groups. Each group received a dose of meloxicam (1 mg/kg) by the IM or oral route. After a 4-week washout period, groups received meloxicam via the other route of administration. Plasma meloxicam concentrations were measured with high-performance liquid chromatography. Data for each bird were analyzed. Estimated values of selected pharmacokinetic parameters were compared by use of a linear mixed-effects ANOVA. Pooled concentration-time profiles for each route of administration were analyzed to examine the influence of body weight on pharmacokinetics. RESULTS Mean ± SD maximum plasma concentration was 1.00 ± 0.88 μg/mL after oral administration. This was approximately 15% of the mean maximum plasma concentration of 5.50 ± 2.86 μg/mL after IM administration. Mean time to maximum plasma concentration was 1.33 ± 1.32 hours after oral administration and 0.28 ± 0.17 hours after IM administration. Mean half-life of the terminal phase after oral administration (3.83 ± 2.64 hours) was approximately twice that after IM administration (1.83 ± 1.22 hours). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the extent and rate of meloxicam absorption were less after oral administration than after IM administration. Intramuscular administration resulted in a short period during which mean plasma concentrations met or exceeded reported efficacious analgesic concentrations in other species, whereas oral administration did not. These results suggested that higher doses may be required for oral administration.

Objective-To evaluate antinociceptive effects and pharmacokinetics of butorphanol tartrate after IM administration to American kestrels (Falco sparverius). Animals-Fifteen 2- to 3-year-old American kestrels (6 males and 9 females). Procedures-Butorphanol (1, 3, and 6 mg/kg) and saline (0.9% NaCl) solution were administered IM to birds in a crossover experimental design. Agitation-sedation scores and foot withdrawal response to a thermal stimulus were determined 30 to 60 minutes before (baseline) and 0.5, 1.5, 3, and 6 hours after treatment. For the pharmacokinetic analysis, butorphanol (6 mg/kg, IM) was administered in the pectoral muscles of each of 12 birds. Results-In male kestrels, butorphanol did not significantly increase thermal thresholds for foot withdrawal, compared with results for saline solution administration. However, at 1.5 hours after administration of 6 mg of butorphanol/kg, the thermal threshold was significantly decreased, compared with the baseline value. Foot withdrawal threshold for female kestrels after butorphanol administration did not differ significantly from that after saline solution administration. However, compared with the baseline value, withdrawal threshold was significantly increased for 1 mg/kg at 0.5 and 6 hours, 3 mg/kg at 6 hours, and 6 mg/kg at 3 hours. There were no significant differences in mean sedation-agitation scores, except for males at 1.5 hours after administration of 6 mg/kg. Conclusion and Clinical Relevance-Butorphanol did not cause thermal antinociception suggestive of analgesia in American kestrels. Sex-dependent responses were identified. Further studies are needed to evaluate the analgesic effects of butorphanol in raptors.

Objective- To compare pharmacokinetics after a single IM or SC injection of ceftiofur crystalline-free acid (CCFA) to bearded dragons (Pogona vitticeps). Animals- 8 adult male bearded dragons. Procedures- In a preliminary experiment, doses of 15 and 30 mg/kg, SC, were compared in 2 animals, and 30 mg/kg resulted in a more desirable pharmacokinetic profile. Then, in a randomized, complete crossover experimental design, each bearded dragon (n = 6) received a single dose of 30 mg of CCFA/kg IM or SC; the experiment was repeated after a 28-day washout period with the other route of administration. Blood samples were collected at 10 time points for 288 hours after injection. Plasma concentrations of ceftiofur and desfuroylceftiofur metabolites were measured via reverse-phase high-performance liquid chromatography. Data were analyzed with a noncompartmental model. Results-No adverse effects were observed. Plasma concentrations greater than a target minimum inhibitory concentration of 1 μg/mL were achieved by 4 hours after administration by both routes. Mean plasma concentrations remained > 1 μg/mL for > 288 hours for both routes of administration. Conclusions and Clinical Relevance-A single dose of CCFA (30 mg/kg) administered IM or SC to bearded dragons yielded plasma concentrations of ceftiofur and its metabolites > 1 μg/mL for > 288 hours. The SC route would be preferred because of less variability in plasma concentrations and greater ease of administration than the IM route. Future studies should include efficacy data as well as evaluation of the administration of multiple doses.

Objective: To evaluate the pharmacokinetics of nalbuphine decanoate after IM administration to Hispaniolan Amazon parrots (Amazona ventralis). Animals: 9 healthy adult Hispaniolan Amazon parrots of unknown sex. Procedures: Nalbuphine decanoate (37.5 mg/kg) was administered IM to all birds. Plasma samples were obtained from blood collected before (time 0) and 0.25, 1, 2, 3, 6, 12, 24, 48, and 96 hours after drug administration. Plasma samples were used for measurement of nalbuphine concentrations via liquid chromatography–tandem mass spectrometry. Pharmacokinetic parameters were estimated with computer software. Results: Plasma concentrations of nalbuphine increased rapidly after IM administration, with a mean concentration of 46.1 ng/mL at 0.25 hours after administration. Plasma concentrations of nalbuphine remained > 20 ng/mL for at least 24 hours in all birds. The maximum plasma concentration was 109.4 ng/mL at 2.15 hours. The mean terminal half-life was 20.4 hours. Conclusions and Clinical Relevance: In Hispaniolan Amazon parrots, plasma concentrations of nalbuphine were prolonged after IM administration of nalbuphine decanoate, compared with previously reported results after administration of nalbuphine hydrochloride. Plasma concentrations that could be associated with antinociception were maintained for 24 hours after IM administration of 37.5 mg of nalbuphine decanoate/kg. Safety and analgesic efficacy of nalbuphine treatments in this species require further investigation to determine the potential for clinical use in pain management in psittacine species.

Objective: To determine pharmacokinetic and pharmacodynamic properties of midazolam after IV and IM administration in alpacas. Animals: 6 healthy alpacas. Procedures: Midazolam (0.5 mg/kg) was administered IV or IM in a randomized crossover design. Twelve hours prior to administration, catheters were placed in 1 (IM trial) or both (IV trial) jugular veins for drug administration and blood sample collection for determination of serum midazolam concentrations. Blood samples were obtained at intervals up to 24 hours after IM and IV administration. Midazolam concentrations were determined by use of tandem liquid chromatography–mass spectrometry. Results: Maximum concentrations after IV administration (median, 1,394 ng/mL [range, 1,150 to 1,503 ng/mL]) and IM administration (411 ng/mL [217 to 675 ng/mL]) were measured at 3 minutes and at 5 to 30 minutes, respectively. Distribution half-life was 18.7 minutes (13 to 47 minutes) after IV administration and 41 minutes (30 to 80 minutes) after IM administration. Elimination half-life was 98 minutes (67 to 373 minutes) and 234 minutes (103 to 320 minutes) after IV and IM administration, respectively. Total clearance after IV administration was 11.3 mL/min/kg (6.7 to 13.9 mL/min/kg), and steady-state volume of distribution was 525 mL/kg (446 to 798 mL/kg). Bioavailability of midazolam after IM administration was 92%. Peak onset of sedation occurred at 0.4 minutes (IV) and 15 minutes (IM). Sedation was significantly greater after IV administration. Conclusions and Clinical Relevance: Midazolam was well absorbed after IM administration, had a short duration of action, and induced moderate levels of sedation in alpacas.

Objective: To compare anesthetic, analgesic, and cardiorespiratory effects in dogs after IM administration of dexmedetomidine (7.5 μg/kg)–butorphanol (0.15 mg/kg)–tiletamine-zolazepam (3.0 mg/kg; DBTZ) or dexmedetomidine (15.0 μg/kg)-tramadol (3.0 mg/kg)-ketamine (3.0 mg/kg; DTrK) combinations. Animals: 6 healthy adult mixed-breed dogs. Procedures: Each dog received DBTZ and DTrK in a randomized, crossover-design study with a 5-day interval between treatments. Cardiorespiratory variables and duration and quality of sedation-anesthesia (assessed via auditory stimulation and sedation-anesthesia scoring) and analgesia (assessed via algometry and electrical nerve stimulation) were evaluated at predetermined intervals. Results: DBTZ or DTrK induced general anesthesia sufficient for endotracheal intubation ≤ 7 minutes after injection. Anesthetic quality and time from drug administration to standing recovery (131.5 vs 109.5 minutes after injection of DBTZ and DTrK, respectively) were similar between treatments. Duration of analgesia was significantly longer with DBTZ treatment, compared with DTrK treatment. Analgesic effects were significantly greater with DBTZ treatment than with DTrK treatment at several time points. Transient hypertension (mean arterial blood pressure > 135 mm Hg), bradycardia (heart rate < 60 beats/min), and hypoxemia (oxygen saturation < 90% via pulse oximetry) were detected during both treatments. Tidal volume decreased significantly from baseline with both treatments and was significantly lower after DBTZ administration, compared with DTrK, at several time points. Conclusions and Clinical Relevance: DBTZ or DTrK rapidly induced short-term anesthesia and analgesia in healthy dogs. Further research is needed to assess efficacy of these drug combinations for surgical anesthesia. Supplemental 100% oxygen should be provided when DBTZ or DTrK are used.

Objective-To determine efficacy of a modified-live virus (MLV) vaccine containing bovine viral diarrhea virus (BVDV) 1a and 2a against fetal infection in heifers exposed to cattle persistently infected (PI) with BVDV subtype 1 b. Animals-50 heifers and their fetuses. Procedures-Susceptible heifers received a placebo vaccine administered IM or a vaccine containing MLV strains of BVDV1a and BVDV2a administered IM or SC. On day 124 (64 to 89 days of gestation), 50 pregnant heifers (20 vaccinated SC, 20 vaccinated IM, and 10 control heifers) were challenge exposed to 8 PI cattle. On days 207 to 209, fetuses were recovered from heifers and used for testing. Results-2 control heifers aborted following challenge exposure; both fetuses were unavailable for testing. Eleven fetuses (8 control heifers and 1 IM and 2 SC vaccinates) were positive for BVDV via virus isolation (VI) and for BVDV antigen via immunohistochemical analysis in multiple tissues. Two additional fetuses from IM vaccinates were considered exposed to BVDV (one was seropositive for BVDV and the second was positive via VI in fetal tissues). A third fetus in the SC vaccinates was positive for BVDV via VI from serum alone. Vaccination against BVDV provided fetal protection in IM vaccinated (17/20) and SC vaccinated (17/20) heifers, but all control heifers (10/10) were considered infected. Conclusions and Clinical Relevance-1 dose of a BVDV1a and 2a MLV vaccine administered SC or IM prior to breeding helped protect against fetal infection in pregnant heifers exposed to cattle PI with BVDV1b.

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.

Eighteen dogs undergoing lateral thoracotomy at the left fifth intercostal space were randomly assigned to 1 of 3 postoperative analgesic treatment groups of 6 dogs each as follows: group A, morphine, 1.0 mg/kg of body weight, IM; group B, 0.5% bupivacaine, 1.5 mg/kg given interpleurally; and group C, morphine, 1.0 mg/kg given interpleurally. Heart rate, respiratory rate, arterial blood pressure, arterial blood gas tensions, alveolar-arterial oxygen differences, rectal temperature, pain score, and pulmonary mechanics were recorded hourly for the first 8 hours after surgery, and at postoperative hours 12, 24, and 48. These values were compared with preoperative (control) values for each dog. Serum morphine and cortisol concentrations were measured at 10, 20, and 30 minutes, hours 1 to 8, and 12 hours after treatment administration . All dogs had significant decreases in pHa, PaO2, and oxygen saturation of hemoglobin, and significant increases in PaCO2 and alveolar-arterial oxygen differences in the postoperative period, but these changes were less severe in group-B dogs. Decreases of 50% in lung compliance, and increases of 100 to 200% in work of breathing and of 185 to 383% in pulmonary resistance were observed in all dogs after surgery. Increases in work of breathing were lower, and returned to preoperative values earlier in group-B dogs. The inspiratory time-to-total respiratory time ratio was significantly higher in group-B dogs during postoperative hours 5 to 8, suggesting improved analgesia. Blood pressure was significantly lower in group-A dogs for the first postoperative hour. Significant decreases in rectal temperature were observed in all dogs after surgery, and hypothermia was prolonged in dogs of groups A and C. Significant differences in pain score were not observed between treatment groups. Cortisol concentration was high in all dogs after anesthesia and surgery, and was significantly increased in group-B dogs at hours 4 and 8. Significant differences in serum morphine concentration between groups A and C were only observed 10 minutes after treatment administration. In general, significant differences in physiologic variables between groups A and C were not observed. Results of the study indicate that anesthesia and thoracotomy are associated with significant alterations in pulmonary function and lung mechanics. Interpleurally administered bupivacaine appears to be associated with fewer blood gas alterations and earlier return to normal of certain pulmonary function values. Interpleural administration of morphine does not appear to provide any advantages, in terms of analgesia or pulmonary function, compared with its IM administration.

Milk antimicrobial residues are a serious concern for the dairy industry. Residues of the tetracycline family of antimicrobials have been reported in market milk by investigators, using radioimmunoassay and microbial receptor technology (hereafter referred to as the Charm II test). In response to these reports, an investigation was conducted to determine the potential of 3 extra-label routes of oxytetracycline (OTC) administration to cause milk residues above the Food and Drug Administration safe value of 30 parts per billion (ppb). Lactating Holstein cows were administered OTC once by use of 1 of 3 routes: IV at 16.5 mg/kg of body weight (n = 6); IM at 11 mg/kg (n = 6); and intrauterine (IU) at 2 g in 500 ml of saline solution/cow (n = 6). Duplicate milk samples were collected at the milking prior to drug administration and for the next 13 milkings at 12-hour intervals. Concentrations of OTC in milk samples were analyzed by use of the Charm II test for tetracyclines (limit of OTC detection, approx 5 ppb) and were compared with concentrations determined by use of a high-performance liquid chromatography (HPLC) method (lower limit of OTC quantitation, approx 2 ppb). The potential for milk OTC residues above the Food and Drug Administration safe value of 30 ppb after treatment was considerably greater for the IV and IM routes, compared with the IU route. Mean peak OTC concentrations in milk at the first milking after treatment for the HPLC and Charm II tests were approximately 3,700 to 4,200 ppb for the IV route, 2,200 to 2,600 ppb for the IM route, and 186 to 192 ppb for the IU route, respectively. Pharmacokinetic analysis, based on milk OTC concentrations, indicated that the area under the curve (AUC) and milk maximal concentration (Cmax) differed significantly (P < 0.001) among routes of administration. The AUC was similar for IV and IM administrations; values for both were greater than the AUC for IU administration. The Cmax was greatest for IV, intermediate for IM, and least for IU administration. There were significant (P less than or equal to 0.01) differences in AUC between assay methods (Charm II vs HPLC) for the IV route. Concentrations of OTC in milk determined by the Charm II test were often greater than those determined by HPLC. Administration of OTC to lactating cows via these routes is extra-label drug use. Failure to withhold the product from early milkings of cows administered OTC by the IV or IM route should be considered a potential cause of OTC residues in market milk. Milk from nearly all cows contained OTC (< 30 ppb), the Food and Drug Administration safe level, by 120 hours after OTC administration. Use of appropriate withholding times and antibiotic residue testing is indicated to avoid OTC residues.