Pharmacokinetics of meloxicam after oral administration of a granule formulation to healthy horses

Abstract

Background Nonsteroidal anti‐inflammatory drugs are administered in horses for several systemic diseases. Selective cyclooxygenase‐2 inhibitors are preferred because of lower risk of adverse effects. Several meloxicam formulations have been tested in horses, but a recently marketed granule oral formulation has not been studied. Objective To characterize the pharmacokinetics of a novel granule meloxicam formulation in fasted and fed horses, and to compare pharmacokinetic features with oral suspension and tablets. Animals Seven healthy adult horses. Methods Meloxicam was administered at 0.6 mg/kg in fasted or fed horses. Blood samples were collected for pharmacokinetic analysis, and vital signs, hematology, and biochemistry variables were monitored for 72 hours. Results No adverse effects were detected. Volume of distribution and clearance after intravenous administration of meloxicam were 0.36 L/kg and 29.12 mL/h/kg, respectively, with a 12.39 hours of terminal half‐life. Protein binding was of 97%. Bioavailability was high for every oral formulation, ranging 70%‐110%, without feed effect. Because of a slower absorption, meloxicam after administration of granules had a longer half‐life (24 and 34 hours, fasted and fed, respectively) and mean residence time (31 and 47 hours), than suspension and tablets (ranging 10‐13 and 13‐15 hours, respectively). In addition, the time above therapeutic concentration was higher for the granule formulation than other formulations. Conclusions and Clinical Importance Granule formulation has different PK parameters compared to other oral formulations, which could enable this formulation to be used for different dosage regimens in order to reach a desired clinical effect or decrease the risk of adverse effects.

Analgesia for Sheep in Commercial Production: Where to Next?

“…Meloxicam has received substantial interest in recent years, with 71 separate articles considering its efficacy, pharmacokinetics, pharmacodynamics and toxicity in a range of species included in the current review [ 82 , 86 , 87 , 95 , 133 , 134 , 175 , 176 , 188 , 189 , 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 , 199 , 200 , 201 , 202 , 203 , 235 , 255 , 257 , 258 , 259 , 306 , 307 , 312 , 313 , 314 , 315 , 316 , 317 , 318 , 319 , 320 , 321 , 322 , 323 , 324 , 325 , 326 , 327 , 328 , 329 , …”

“…Half-life 15.4 h [191] 10.69 h [190,192] 14.59-27.54 h [175,176,195,200,201] 10-34 h [202] Iguana: 12.96 h [196] Llama: 22.7 h [197] Pig: 6.83 h [198] MEC MEC * * MEC is based on the minimum dose rate at which suppression of prostaglandin or thromboxane production has been reported. # Data presented relate to RWJ-20142, the active acid metabolite of tepoxalin.…”

“…Meloxicam has received substantial interest in recent years, with 71 separate articles considering its efficacy, pharmacokinetics, pharmacodynamics and toxicity in a range of species included in the current review [82,86,87,95,133,134,175,176,[188][189][190][191][192][193][194][195][196][197][198][199][200][201][202][203]235,255,[257][258][259]306,307,. Meloxicam is considered to be COX-2 selective [306,307,312], and has minimal effects on platelet function, making it suitable for post-operative use [313].…”

Impact of gastrointestinal differences in veterinary species on the oral drug solubility, in vivo dissolution, and formulation of veterinary therapeutics

“…Regarding the other veterinary species, although fed/fasted studies may be published in horses [ 29 ] and swine [ 30 ], species such as cattle, horses, poultry, and swine typically have levels of residual material within their stomachs throughout the day. In nature, horses rarely exist in a fasted state [ 31 ].…”

Preliminary Investigation into a Novel Sustained-Release Formulation of Meloxicam in Sheep (Ovis aries)—Pharmacokinetic Profile

“…Meloxicam possesses various beneficial actions that make it a model NSAID for use in animals, including extended elimination half-life, low gastrointestinal toxicity, suitable oral and injectable absorption rates, and good bioavailability [ 2 , 3 , 4 ]. The pharmacokinetic (PK) profile of meloxicam has been studied in several companion, wildlife, and production species including koalas [ 5 ], guinea pigs [ 6 ], dogs [ 7 ], cats [ 8 ], birds [ 9 ], cattle [ 10 ], horses [ 11 ], and sheep [ 12 , 13 ].…”