American flamingos (Phoenicopertus ruber) are a species commonly kept in captivity. They are particularly prone to mild to severe foot lesions in addition to other conditions that may indicate the need for analgesia.1,2 Appropriate means of pain control are an essential part of the medical management of avian species. The NSAIDs are the class of analgesics most commonly prescribed in small animal medicine because of their anti-inflammatory and antinociceptive effects both peripherally and centrally.3–7 The NSAIDS act by inhibiting COX enzymes, which results in reduced biosynthesis of various prostaglandins and antipyretic, anti-inflammatory, and analgesic effects.6 The COX-1-sparing NSAIDs such as meloxicam exert their effects by selectively inhibiting COX-2 while minimally inhibiting COX-1. It was initially believed that COX-1 enzymes are constitutively expressed in most tissues and cell types and that COX-2 enzymes are induced by inflammatory stimuli and generate prostaglandins that are potent inflammatory mediators.7 However, it has been found that both COX-1 and COX-2 are present in certain inflammatory tissues in mammalian and reptilian species. It has also been suggested that COX-2 may be constitutively present in some tissues and that there are differences between species in the distribution, and possibly function, of COX isoforms.8
Meloxicam is an oxicam NSAID that selectively inhibits COX-2. The COX enzymes are widely distributed in avian tissues and are believed to function both peripherally and centrally in a manner similar to that in mammals.4 Meloxicam is available in injectable and oral formulations, and it is a commonly used analgesic in avian species.4 Published meloxicam doses recommended for birds range from 0.1 to 1.0 mg/kg.3,9–12 Many of the recommended doses for birds have been extrapolated from studies of dogs or are based on clinical experience. Pharmacokinetic studies have revealed that meloxicam metabolism can differ greatly among species. There may be interspecies differences in the relative COX-1 or COX-2 selectivity of certain drugs as well as differences in selectivity between in vivo and in vitro pharmacodynamic assays.7,13 Pharmacokinetic data available for various avian species have revealed variations that may be associated with differences in plasma protein binding and biotransformation pathways.14 Therefore, it is essential to determine pharmacokinetic data for individual avian species.
The pharmacokinetics of meloxicam has been evaluated for Hispaniolan Amazon parrots (Amazona ventralis), red-tailed hawks (Buteo jamaicensis), great horned owls (Bubo virginianus), chickens, ducks, pigeons, vultures, ostriches, turkeys, and parakeets.3,14–18 However, the analgesic efficacy of meloxicam has been evaluated in only a few avian species.3,9 Although it is not possible to extrapolate analgesic efficacy from pharmacokinetic data for American flamingos, the data may be valuable as additional information regarding meloxicam use in avian species becomes available.
To the authors’ knowledge, there have been no data published on the pharmacokinetics of meloxicam after oral and IM administration to American flamingos. The objective of the study reported here was to evaluate pharmacokinetics after oral and IM administration of meloxicam to American flamingos to provide information that may be beneficial in determining clinical dosing regimens in this species.
Materials and Methods
Animals
Fourteen young adult (3 to 6 years old) American flamingos (8 females and 6 males) belonging to a zoological collection were used in the study. Body weight ranged from 2.27 to 4.36 kg. All birds underwent a complete physical examination and blood biochemical evaluation prior to the beginning of the study and were found to be in good health with no medical concerns. No changes were made to the flamingos’ housing arrangements or diet during the study. The birds were kept in a heated building that included a built-in pool area. Misters were activated overnight, and birds had access to a fenced outdoor area during the daytime. Birds had ad libitum access to a commercial pelleted diet formulated for flamingos and a variety of chopped greens. Food was removed at the end of the day preceding drug administration, and the feeding regimen resumed 1 hour after drug administration the subsequent morning. The research protocol was approved by the Institutional Animal Care and Use Committee of the Potawatomi Zoo.
Dosing calculations and target plasma concentrations
A dose of 1 mg of meloxicam/kg was chosen on the basis of published recommendations for avian species (range, 0.1 to 1.0 mg/kg). The high end of this dose range was chosen on the basis of results of previous avian studies that indicated a higher orally administered dose is necessary to induce a desired analgesic effect. Because of the concern for potential adverse effects when using a dose above the recommended range, a dose exceeding 1 mg/kg was not used in this study. The target therapeutic plasma range of meloxicam in flamingos was not known. Therefore, the analgesic plasma meloxicam concentration was estimated to be 3.5 μg/mL on the basis of results of previous studies.3,4
Meloxicam administration and blood collection
Two flamingos (1 male and 1 female) were used to establish an appropriate matrix for collection of blood samples. Each of these birds received a single dose of meloxicama (oral suspension; 1.5 mg/mL) via oral administration. Each dose of meloxicam (1 mg/kg; volume, 2.30 to 2.36 mL) was administered via a 10F red rubber tube, which was followed by administration of 5 mL of water to flush the tube. Ten blood samples (0.30 mL/sample; total volume, < 1.0% of body weight) were collected from each bird at 10 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, and 72 hours after drug administration. The flamingos were manually restrained for venipuncture, and blood was collected from the right or left jugular vein by use of a 1.0-mL syringe and 27-gauge needle.
The remaining 12 flamingos were used in a 2 × 2 crossover design study. A baseline blood sample was collected during a routine annual physical examination performed 7 days prior to the beginning of the study. Each bird was assigned to a group by use of a simple randomization technique (coin toss) and initially (period 1) received a single dose of meloxicam via IM or oral administration (time of meloxicam administration was designated as time 0). Subsequently, the birds received a single dose of meloxicam via the other route of administration (period 2). There was a 4-week washout period between subsequent treatments.
In period 1, 6 flamingos (3 males and 3 females) received a single dose of meloxicam (oral suspension; 1.5 mg/mL) via oral administration. Each dose of meloxicam (1 mg/kg; volume, 1.87 to 2.85 mL) was administered via a 10F red rubber tube, which was followed by administration of 5 mL of water to flush the tube. The remaining 6 flamingos (2 males and 4 females) received a single dose of meloxicamb (injectable solution; 5.0 mg/mL) via IM administration into the left or right pectoral muscle. Each dose of meloxicam (1 mg/kg; 0.45 to 0.87 mL) was administered by use of a 1.0-mL syringe and 25-gauge needle. Ten blood samples (0.30 mL/sample; total volume, < 1.0% of body weight) were collected from each bird at 10 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, and 72 hours after drug administration.
In period 2, the 6 flamingos that received meloxicam via oral administration in period 1 received a single dose of meloxicam via IM administration (1 mg/kg; volume, 0.56 to 0.85 mL) in the manner previously described. The 6 flamingos that received the drug via IM administration in period 1 received a single dose of meloxicam via oral administration (1 mg/kg; volume, 1.51 to 2.91 mL) in the manner previously described. Eight blood samples were collected from each bird at 10 minutes, 30 minutes, and 1, 2, 4, 8, 12, and 24 hours after drug administration.
Blood samples were immediately placed in 1.0-mL lithium heparin microcontainer tubes. Tubes were centrifuged at 2,400 × g for 10 minutes within 60 minutes after blood collection. Plasma was harvested, placed into polypropylene cryogenic vials, and stored at −40°C for shipment to the University of Tennessee College of Veterinary Medicine for analysis.
Measurement of meloxicam concentrations
Analysis of meloxicam in plasma samples was conducted by use of reversed-phase high-performance liquid chromatography. The system consisted of a separation module,c a UV absorbance detector,d and a computer equipped with commercially available software.e Compounds were separated on a C18 columnf (4.6 × 250 mm; 5 μm in diameter) with a 5-μm guard column.g The mobile phase was a 50:50 mixture of 10 mL of glacial acetic acid in 1 L of H2O (pH, 3.0; adjusted with NaOH) and acetonitrile. Flow rate was 1 mL/min. Absorbance was measured at 360 nm.
Meloxicam was extracted from plasma samples by use of liquid-liquid extraction. Frozen plasma samples were thawed and mixed in a vortex device. Then, 100 μL of plasma was transferred to a screw-top tube, and 15 μL of piroxicam (internal standard; 5 μg/mL) was added, which was followed by the addition of 100 μL of 1M HCL and 2 mL of chloroform. Tubes were mixed in a vortex device for 60 seconds and then centrifuged for 20 minutes at 1,070 × g. The organic phase was transferred to a clean glass tube and evaporated to dryness with nitrogen gas. Samples were reconstituted in 250 μL of mobile phase, and a volume of 100 μL was injected into the chromatography system.
Standard curves for plasma analysis were prepared by fortifying untreated plasma with meloxicam to create concentrations that yielded a linear curve over the range of 5 to 1,500 ng/mL. Calibration samples were prepared in the same manner as plasma samples. The lower limit of quantification during validation was 5 ng/mL. Intra-assay and interassay variability ranged from 3% to 10%, and the mean recovery for meloxicam was 89%.
Pharmacokinetic and statistical analysis
Individual plasma concentration data were analyzed by use of a noncompartmental approach with commercially available software.h Estimated values of selected pharmacokinetic parameters were compared by use of a linear mixed-effects ANOVA, assuming a log-linear distribution for the pharmacokinetic parameters and α = 0.05. Additionally, the pooled concentration-time profiles for each administration route were analyzed by use of an NLME compartmental model with commercially available software.i For a dataset that included a small number of subjects from which an appropriate number of samples had been obtained, NLME analysis allowed calculation of preliminary estimates of interindividual pharmacokinetic variability as well as exploration of the potential influence of body weight on pharmacokinetics. Relevance of the inclusion of body weight in the pharmacokinetic model was assessed on the basis of the decrease in interindividual and residual variabilities, assessment of diagnostic plots, and results of the likelihood ratio test, which estimated the significance of the decrease in the −2 log-likelihood function between nested models for α = 0.01.
Results
Each of the birds included in the study was monitored closely the day of and for several days after drug administration and blood collection. Each bird's behavior, amount of activity, and feed consumption were evaluated. None of the birds had detectable changes in activity, behavior, or appetite. No other detectable changes were evident on visual examination.
The mean plasma concentration of meloxicam after administration as a single dose of 1 mg/kg to 14 American flamingos by the oral route and 12 American flamingos by the IM route was plotted (Figure 1). The plasma concentration after IM administration reached the target concentration of 3.5 μg/mL, but then quickly decreased below this concentration within 1 hour after drug administration. The plasma concentration after oral administration did not reach the target concentration.
Mean ± SD plasma concentration of meloxicam at various times after IM administration (dashed line) of a single dose (1 mg/kg) to 12 American flamingos (Phoenicopertus ruber) and oral administration (solid line) of a single dose (1 mg/kg) to 14 American flamingos.
Citation: American Journal of Veterinary Research 78, 3; 10.2460/ajvr.78.3.267
Derived pharmacokinetic parameters after IM and oral administration were summarized (Table 1). No significant effect of period or sequence was detected for any of the parameters. An ANOVA for a crossover study needs to account for potential period and sequence effects. Differences between routes of administration were significant for all pharmacokinetic parameters tested. Mean ± SD maximum plasma concentration was 1.00 ± 0.88 μg/mL after oral administration, which was significantly less than the mean concentration of 5.50 ± 2.86 μg/mL after IM administration. Mean area under the plasma concentration-time curve after oral administration (2.54 ± 1.48 h•μg/mL) was approximately 39% of that after IM administration (5.78 ± 1.88 h•μg/mL). Mean t1/2 of the terminal phase after oral administration (3.83 ± 2.64 hours) was approximately twice that after IM administration (1.83 ± 1.22 hours).
Mean ± SD values determined for 12 American flamingos (Phoenicopertus ruber) after IM administration of a single dose of meloxicam (1 mg/kg) and 14 American flamingos after oral administration of a single dose of meloxicam (1 mg/kg).
| Parameter IM | Oral | P value* | |
|---|---|---|---|
| Cmax (μg/mL) | 5.50 ± 2.86 | 1.00 ± 0.88 | < 0.001 |
| Tmax (h) | 0.28 ± 0.17 | 1.33 ± 1.32 | < 0.001 |
| t1/2 (h) | 1.83 ± 1.22 | 3.83 ± 2.64 | 0.029 |
| V/F (mL/kg) | 530 ± 487 | 2,420 ± 1,167 | < 0.001 |
| AUC0-∞ (h·μg/mL) | 5.78 ± 1.88 | 2.54 ± 1.48 | < 0.001 |
| CL/F (mL/h/kg) | 190 ± 67 | 590 ± 518 | < 0.001 |
| MRT0-∞ (h) | 1.77 ± 1.41 | 4.80 ± 2.82 | < 0.001 |
Values were considered significant at P < 0.05.
AUC0-∞ = Area under the concentration-time curve from time 0 extrapolated to infinity. Cmax = Maximum concentration. MRT0-∞ = Mean residence time from time 0 extrapolated to infinity. t1/2 = Terminal elimination half-life. Tmax = Time to maximum concentration.
Results of the NLME for IM data were summarized (Table 2). The addition of body weight to the pharmacokinetic model increased the correlation between observed and predicted values for plasma concentration. This illustrated the relevance of body weight in this model. For IM administration, the structural model that best fit the data included biexponential decay with first-order absorption. The best fit for distribution of individual parameters was a log-normal model; therefore, the pharmacokinetic data were modeled on an exponential scale. The selected residual model was proportional. The final model included body weight (centered on the mean) as an explanatory covariate for CL/F, Vc/F, Vp/F, and Q/F as follows:
Results for NLME analysis after IM administration of meloxicam (1 mg/kg) to 12 American flamingos.
| Model without covariates | Model with body weight as a covariate | |||
|---|---|---|---|---|
| Parameter | Estimate | IIV (%) | Estimate | IIV (%) |
| Kapop | 20.5 | NA | 63.3 | NA |
| CL/Fpop | 0.163 | 27.8 | 0.159 | 16.1 |
| CL/Fβ | NA | NA | −0.316* | NA |
| Vc/Fpop | 0.142 | 51.3 | 0.135 | 17.2 |
| Vc/Fβ | NA | NA | −0.336* | NA |
| Q/Fpop | 0.026 | 67.5 | 0.026 | 59.9 |
| Q/Fβ | NA | NA | −0.865† | NA |
| Vp/Fpop | 0.228 | 106.0 | 0.312 | 51.5 |
| Vp/Fβ | NA | NA | −1.370* | NA |
| Residual error | NA | 17.0 | NA | 17.0 |
The addition of body weight (centered on the mean) to the pharmacokinetic model increased the correlation between observed and predicted plasma concentration values; this illustrated the relevance of body weight in this model. The β parameters (ie, slope) quantitatively describe the effect for body weight on each of the pharmacokinetic parameters; the negative value indicated a decrease in these parameters as body weight increased.
Value is significant (P < 0.001).
Value is significant (P = 0.002).
CL/Fβ = Slope for CL/F. CL/Fpop = Population value for CL/F. IIV = Interindividual variability estimate. Kapop = Population value for the absorption rate constant. NA = Not applicable. Q/Fβ = Slope for Q/F. Q/Fpop = Population value for Q/F. Vc/Fβ = Slope for Vc/F. Vc/Fpop = Population value for Vc/F. Vp/Fβ = Slope for Vp/F. Vp/Fpop = Population value for Vp/F.
where θi is the value of the pharmacokinetic parameter for an individual bird i, θμ is the mean population value of the pharmacokinetic parameter, e is the base of the natural logarithm, βθ is the parameter that relates individual body weight (centered on the mean) with the corresponding pharmacokinetic parameter, BWcent is body weight centered on the mean, and η(θ,i) is the deviation in the value of the pharmacokinetic parameter for an individual bird i with respect to the mean value.
The MVOF decreased significantly from −13.83 to −51.74 when the covariate BWcent was included in the model for CL/F, Vc/F, Vp/F, and Q/F (it also did so for each parameter separately). The MVOF was used to compare the adequacy of competing regression models (eg, one model including BWcent and the other not including BWcent as a covariate for a given pharmacokinetic parameter). Because the full model (the one including the covariate) had a significant decrease in the MVOF in comparison with the reduced model (the one not including the covariate), then the full model was the most appropriate. In other words, inclusion of the covariate in the model explained a significantly larger portion of the data, compared with results for the model that did not include the covariate. The inclusion of BWcent in the pharmacokinetic model as an explanatory covariate was significant (P < 0.01) for CL/F, Vc/F, Vp/F, and Q/F. Although residual variability was not affected by the inclusion of BWcent in the model, interindividual variability decreased from 27.8% to 16.1% for CL/F, from 51.3% to 17.2% for Vc/F, from 106% to 51% for Vp/F, and from 67.5% to 59.9% for Q/F.
When the NLME analysis was repeated with the doses reported as the number of milligrams, rather than the number of milligrams per kilogram, no significant relationship was found between body weight and CL/F, Vc/F, Vp/F, or Q/F. Interestingly, the interindividual variabilities for CL/F and Vc/F were much lower (17% and 19%, respectively) than the values for the same parameters when the dose was reported as the number of milligrams per kilogram (28% and 51%, respectively).
An NLME analysis for oral administration data was also conducted. The model that best fit the data included biexponential decay with first-order absorption. The best fit for distribution of individual parameters was a log-normal model, and the selected residual model was proportional. No relationship was detected between body weight and any pharmacokinetic parameter. As expected, interindividual and residual variabilities of pharmacokinetic parameters were higher after oral administration than after IM administration, except for the absorption rate constant.
Discussion
In the study reported here, meloxicam was found to have a short t1/2 in American flamingos after administration by the oral and IM routes. Mean ± SD elimination t1/2 was 1.83 ± 1.22 hours and 3.83 ± 2.64 hours after IM and oral administration, respectively. Results of the present study were consistent with the rapid t1/2 of meloxicam reported in other avian species.14,15 In a study14 that involved administration of a single dose of meloxicam (0.5 mg/kg) IV and orally to red-tailed hawks and great horned owls, the mean elimination t1/2 was 0.49 ± 0.5 hours and 0.78 ± 0.52 hours, respectively, after IV administration and 3.97 ± 3.32 hours and 5.07 ± 4.5 hours, respectively, after oral administration. Even though the dose of meloxicam used in that study was half the dose used in the present study, the t1/2 for red-tailed hawks was similar to that for flamingos, whereas the t1/2 for great horned owls was greater than that for flamingos. The t1/2 values for red-tailed hawks, great horned owls, and American flamingos are much shorter than the mean elimination t1/2 reported for Hispaniolan Amazon parrots, which was 15.1 ± 7.7 hours and 15.8 ± 8.6 hours after IM and oral administration, respectively.4 Interestingly, investigators of a study15 conducted to evaluate pharmacokinetics of meloxicam after IV administration at a dose of 0.5 mg/kg to 5 avian species reported the elimination t1/2 had a negative correlation with body weight, with the largest bird having the shortest t1/2. For that study,15 the mean t1/2 value was 3.29 ± 0.58 hours for chickens, 2.70 ± 1.03 hours for pigeons, 1.02 ± 0.19 hours for turkeys, 0.73 ± 0.12 hours for ducks, and 0.52 ± 0.31 hours for ostriches.
Pharmacokinetic studies in various avian species have revealed great variation in the elimination t1/2 among species. This may indicate that different dosing regimens may be necessary for the various species. Data for avian species indicate that the t1/2 of meloxicam is overall much shorter than that in some mammalian species, such as dogs19 (24 hours) or bottlenose dolphins (Tursiops truncates [up to 70 hours]).20 The large interspecies differences suggest that the recommendation for once-daily administration of meloxicam may not be appropriate for all species.
In the present study, a target mean meloxicam plasma concentration of 3.5 μg/mL was used on the basis of results for studies3,4 in Hispaniolan parrots. In those studies,3,4 investigators found that a meloxicam dose of 1.0 mg/kg correlated with a plasma meloxicam concentration of 3.5 μg/mL, which was determined to be a concentration that provides relief for arthritic pain in that species. The investigators also found that the IV and IM routes of administration resulted in rapid achievement of the target plasma concentration, which was maintained for > 12 hours. However, the oral route resulted in slow achievement of the target plasma concentration, and the plasma concentration was less than the target concentration by 12 hours after administration. This suggests that higher drug doses are needed for oral administration to provide blood concentrations equivalent to concentrations after IV or IM administration. In another study,9 domestic pigeons (Columba livia) received a dose of meloxicam (1 mg/kg, PO) after analgesic effects were not achieved at lower doses. In that study,9 pharmacokinetic data were not obtained for the pigeons to correlate with the various doses of meloxicam. Although no adverse effects were detected in the pigeons after receiving the 2 mg/kg dose, susceptibility to the toxic effects of meloxicam can potentially differ among species. Therefore, a dose higher than the recommended range of 0.1 to 1.0 mg/kg was not used for American flamingos of the present study because the safety for higher doses of meloxicam has not been established in flamingos.
Other factors should also be considered when determining the analgesic efficacy of meloxicam in avian species. Most NSAIDs have a high degree of protein binding that can cause a relatively low volume of distribution into the interstitial fluid. This facilitates passage into areas of inflammation with leakage of plasma proteins into exudate.21 It is therefore possible that analgesic effects remain after the drug is no longer detectable in the plasma.22 Differences in plasma protein binding and biotransformation pathways could potentially contribute to differences observed in the pharmacokinetic parameters of mammalian and avian species. For instance, in the study14 that involved red-tailed hawks and great horned owls, the volume of distribution of meloxicam was higher for red-tailed hawks, but the blood concentrations were higher for great horned owls. Because these are 2 closely related avian species, large differences were not expected for the pharmacokinetic data. One suggested explanation was that because the volume of distribution describes distribution of the drug from the blood into the body, great horned owls possibly could have protein binding that limits the drug's distribution to the tissues.14
Interestingly, the pharmacokinetic data obtained in the present study for American flamingos indicated that both the extent and rate of absorption of meloxicam were lower after oral administration than after IM administration. The rate of absorption after oral administration appeared to be slow enough to result in an increased time to the maximum concentration (1.33 and 0.28 hours for oral and IM administration, respectively) and t1/2, compared with results after IM administration. This may have been the result of a flip-flop phenomenon, which occurs when the absorption process is slow enough to result in measured concentrations during all phases of the concentration-time profile (including the decay phase). The elimination t1/2 is determined by clearance and the volume of distribution of a drug and is typically the same irrespective of the route of administration. Flip-flop kinetics has also been described for llamas and other ruminants, most likely because the rumen delays absorption of the drug from the gastrointestinal tract.23 The cause of this phenomenon in American flamingos is unclear.
The NLME results indicated that when meloxicam was administered IM as a single 1 mg/kg dose to American flamingos, exposure was substantially higher in larger birds (body weight ranged from 2.27 to 4.36 kg). Exposure is the plasma concentration-time profile as defined by the area under the curve. The significant relationship between body weight and both clearance and volume parameters for extravascular administration suggested that differences in drug absorption among birds of various body weights may have been responsible for the observed variability in exposure. As a matter of fact, when the NLME analysis was repeated with the doses reported in milligrams (rather than in milligrams per kilogram), no relationship was found between body weight and clearance or volume parameters. Furthermore, the interindividual variability in CL/F and Vc/F was much lower when the doses were reported in milligrams than in milligrams per kilogram. On the basis of these results, larger birds would have been expected to have an increased extent of absorption. This could have been a result of an increase in the diffusion surface for a given injection volume in larger birds, but the injection volumes were normalized on the basis of body weight in the present study.
The present study had several limitations that should be considered. The target meloxicam plasma concentration of 3.5 μg/mL was used, although the authors acknowledge that this was not an established plasma target concentration for meloxicam in American flamingos. The target range for meloxicam plasma concentrations in other species, such as horses, reportedly is > 0.2 μg/mL.24 There is little data to correlate meloxicam pharmacokinetic data with pharmacodynamic data in any avian species. Ideally, the present study would have included a pharmacodynamic analysis in conjunction with the pharmacokinetic analysis; however, these American flamingos were part of a zoological collection, and thus this was not possible. Therefore, data available for an avian species given a 1 mg/kg dose of meloxicam were used as a reference.
In addition, the SD values obtained were quite large, which is consistent with meloxicam pharmacokinetics in other avian species. The calculated number of birds was based on a 20% acceptance range for differences between parameters, 5% actual estimated difference, 80% power, α of 0.05, and assumed coefficient of variation of 35% for the area under the concentration-time curve. The SD values were determined only after the study was completed. Parameters were compared by use of a linear mixed-effects ANOVA that accounted for period, sequence, and effect, which resulted in significant differences between routes of administration.
Additionally, although the American flamingos included in the present study did not have adverse effects following drug administration, as determined on the basis of clinical observation, none of the birds were evaluated histologically for evidence of renal toxicosis or muscle necrosis at the site of IM administration. Meloxicam appears to be safe for use in various avian species because no fatalities associated with meloxicam use were reported in a survey of 750 birds of 60 species.18 However, tissue necrosis was reported at the injection sites after IM administration of meloxicam to Coturnix quail.2,19 Therefore, additional studies on the safety of using meloxicam by any route of administration in American flamingos is also warranted.
Results of the study reported here provided pharmacokinetic parameters for American flamingos that received meloxicam at a dose of 1 mg/kg by both the oral and IM routes of administration. Although the analgesic efficacy of meloxicam in American flamingos could not be determined from these data, results indicated that meloxicam was cleared rapidly, which is consistent with data for several other avian species. To determine optimal dosing and treatment intervals necessary to ensure concentrations for clinical efficacy, further studies of American flamingos that combine pharmacodynamics with pharmacokinetics and safety trials are recommended.
Acknowledgments
Presented in abstract form at the 46th Annual International Association for Aquatic Animal Medicine Conference, Chicago, April 2015.
ABBREVIATIONS
| CL/F | Total body clearance as a function of bioavailability |
| COX | Cyclooxygenase |
| MVOF | Minimum value of the objective function |
| NLME | Nonlinear mixed effects |
| Q/F | Intercompartmental clearance as a function of bioavailability |
| t1/2 | Half-life |
| Vc/F | Volume of the central compartment after IM or oral drug administration as a function of bioavailability |
| Vp/F | Volume of the peripheral compartment after IM or oral drug administration as a function of bioavailability |
Footnotes
Metacam oral suspension, Boerhinger Ingelheim Inc, St Joseph, Mo.
Metacam solution for injection, Boerhinger Ingelheim Inc, St Joseph, Mo.
2695 separations module, Waters, Milford, Mass.
2487 UV absorbance detector, Waters, Milford, Mass.
Empower 3, Waters, Milford, Mass.
C18 Xbridge, Waters, Milford, Mass.
Xbridge guard column, Waters, Milford, Mass.
Phoenix software, version 6.3.0.395, Certara USA Inc, Princeton, NJ.
Lixoft SAS, Orsay, France.
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