Pharmacokinetics and Safety of Intramuscular Meloxicam in Zebra Finches (Taeniopygia guttata)

Abstract

Zebra finches (Taeniopygia guttata) are songbirds that often undergo surgical procedures as part of research into learning and memory; these surgeries include those for intracranial injections and cranial implants. At our institution, birds receive subcutaneous lidocaine (a local anesthetic) and intramuscular buprenorphine (an opioid analgesic) preoperatively, with buprenorphine continued every 12 h postoperatively for 2 to 3 d. More recently, the possibility of substituting meloxicam (a COX2-selective NSAID) for buprenorphine, or adding meloxicam to the existing analgesia regimen for a more multimodal approach, has been suggested. The enhanced pain control derived from using lidocaine, buprenorphine, and meloxicam could be of particular benefit in finch surgeries that are particularly invasive or complicated. However, although meloxicam is the most popular NSAID used in birds, 7 the optimal dose and frequency for zebra finches are unknown. Publications that describe the pharmacokinetics of meloxicam in diverse, nonpasserine avian species (doses ranging from 0.5 to 3.0 mg/kg IM, IV, SC, or PO) 1,2,6,8-10,12-15,18 report a wide range of elimination half-lifes (t 1/2 ). For example, vultures dosed once with 2 mg/ kg meloxicam IM had an elimination t 1/2 of 0.42 h, 15 whereas African grey parrots had a t 1/2 of 35.3 h after a dose of 1 mg/kg IM. 12 Such results have caused numerous authors to emphasize the need for species-specific pharmacokinetic analyses before administering meloxicam to any bird. Additional concerns when giving an NSAID include the potential for renal damage, as reflected in uric acid levels and kidney histology, 16,17 and for gastrointestinal effects; with intramuscular administration, another potential sequela is necrosis at the injection site. As is often the case in laboratory animal medicine, giving meloxicam to zebra finches constitutes an extralabel use.We performed a study using healthy, adult zebra finches that entailed the administration of 1 or 2 mg/kg meloxicam intramuscularly to help elucidate an optimal dosing regimen, as well as to reveal any evidence of toxicity. Pharmacokinetic parameters were assessed after a single dose, whereas biochemical analytes, Hct, and histology were evaluated after multiple doses. Our findings are the first to characterize the use of meloxicam in a passerine species. Materials and MethodsAnimals. Male (n = 46) and female (n = 46) wildtype zebra finches older than 90 d were involved in the study; all the birds were in good health clinically and had adequate body condition scores. Finches were maintained in an AAALAC-accredited facility under a 12:12-h light:dark cycle, with temperatures from 73 to 77 °F (22.8 to 25.0 °C) and ambient humidity set at 30% to 70%. The main diet was a fortified millet-canary grass seed-oat mix (Supreme Fortified Daily Diet: Finch, Kaytee Products, Chilton, WI), to which a high-protein supplement (High Potency Mash, Harrison's Bird Foods, HBD International, Brentwood, TN), moistened and mixed with minced hard-boiled eggs, wa...

Pharmacokinetics of meloxicam, carprofen, and tolfenamic acid after intramuscular and oral administration in Japanese quails (Coturnix coturnix japonica)

“…However, the obvious differences in t 1/2ʎz of MLX, CRP, and TA have been reported among species. After IM and oral administration in quails, the t 1/2ʎz of MLX was 1.55 and 1.59 h, respectively, which was similar to that previously reported in flamingos (oral: 1.83 h, Lindemann et al, 2016), shorter than that previously reported in parrots (IM: 15.1-35.3 h, oral: 15.8-33.6 h, Molter et al, 2013;Montesinos et al, 2016), penguins (IM: 31.87 h, oral: 28.59 h, Morrison et al, 2018), zebra finches (IM: 3.24 h, Miller et al, 2019), hawks (oral: 3.97 h), owls (oral: 5.07 h, Lacasse et al, 2013), and geese (oral: 3.65 h; Sartini et al, 2020), and longer than that previously reported in cockatiels (oral: 0.90 h, Dhondt et al, 2017) and vultures (IM: 0.42 h, oral: 0.32 h, Naidoo et al, 2008). After IM and oral administration in quails, the t 1/2ʎz of TA was 1.51 and 1.25 h, respectively, which was shorter than that previously reported in mammals (IM: 2.61-8.22 h, oral: 5.13-19.7, Corum et al, 2018;Sidhu et al, 2005;Sidhu et al, 2006;Dinakaran & Dumka, 2013) and reptiles (IM: 22.49-53.69 h, Corum et al, 2019a;Raweewan et al, 2020).…”

“…After IM administration of MLX at a dose of 1 mg/kg in quails, the C max (4.27 μg/mL), and T max (0.33 h) were lower and shorter, respectively, than those previously reported in parrots (C max : 8.32-10.5 μg/mL, T max : 0.5-1.4 h) and zebra finches (C max : 8.56 μg/mL, T max : 0.5 h) (Miller et al, 2019;Molter et al, 2013;Montesinos et al, 2016). The C max varied from 0.1 to 10.84 μg/mL and T max from 0.5 to 13.2 h after the oral administration of MLX to different bird species (parrots, penguins, cockatiels, and flamingos) at a dose of 1 mg/ kg (Dhondt et al, 2017;Lindemann et al, 2016;Molter et al, 2013;Montesinos et al, 2016;Morrison et al, 2018).…”

“…In parrots, oral administration of MLX at a dose of 0.5 mg/kg for 14 days (q 12 h) and at a dose of 1.6 mg/kg for 15 days (q 12 h), has not cause hematological, biochemical, or histopathological changes (Dijkstra et al, 2015; Montesinos et al, 2015). While MLX does not alter the renal histopathology in zebra finches (1–2 mg/kg IM, q 12 h for 4 days), the degeneration and dilation of renal tubules have been reported in budgerigars (0.1 mg/kg IM for 3–5 days) (Miller et al, 2019; Pereira & Werther, 2007). The safety of meloxicam in birds may be due to potent COX−2 inhibitor activity of meloxicam with the COX‐1/COX‐2 ratio of >1 (Hunter et al, 2015; Kay‐Mugford et al, 2000).…”

“…In the present study, IM and oral routes were preferred because they are the common route of administration in quails. Although oral administration is highly preferred in birds, it may result in poor absorption and variable bioavailability (Miller et al, 2019). IM administration has been considered as a viable alternative to oral administration due to the rapid onset of absorption and high bioavailability.…”

Pharmacokinetics of the Anti-Inflammatory Drug Meloxicam after Single 1.5 mg/kg Intramuscular Administration to Undulate Skates (Raja undulata)

“…Meloxicam elimination was also fast in the undulate skates, with a relatively short t 1/2 β (3.55 h) when compared to other mammalian species, such as rabbits (6.1 h) or horses (8.5 h) [ 14 , 27 ]. The elimination half-life was, however, within range of that reported in teleost species, such as tilapia (1.59 h) and trout (4.55 h), reptile species, such as the loggerhead sea turtle ( Caretta caretta Linnaeus, 1758) (3.26 h), and avian species, such as the zebra finch ( Taeniopygia guttata Vieillot, 1817) (3.24 h) [ 12 , 14 , 28 , 29 ]. Previous studies performed with meloxicam in avian species showed that interspecific and interindividual variations in Phase I system enzymes, such as cytochromes P450 (CYPs), can result in longer half-lives of metabolized NSAIDs [ 7 ].…”