Preliminary Evaluation of Sustained-release Compared with Conventional Formulations of Meloxicam in Sheep (Ovis aries)

摘要

Sustained-release (SR) drugs refine current analgesic regimens by alleviating the need for multiple sessions of handling and restraint and by reducing the local tissue irritation that can occur due to repeated injections. Although a variety of SR drugs are already used in lab animal medicine, no studies exist that evaluate the suitability of an SR NSAID in sheep. This study used HPLC-MS to measure the plasma concentrations of 2 formulations of meloxicam-conventional and SRM- after subcutaneous administration in 6 adult ewes. Blood was collected at 0, 4, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, and 168 h after injection. In addition, physical exams, urinalysis, and biochemical analysis were performed at 0, 24, 48, and 120 h after dosage. Peak plasma concentrations were 1057 +/- 433 ng/mL at 4 +/- 0 h for conventional meloxicam and 3238 +/- 1480 ng/mL at 6.7 +/- 4.1 h for SR meloxicam (SRM). Elimination half-lives were 12.1 +/- 4.2 for CM and 15.2 +/- 2.4 h for SRM. One sheep had an episode of acute renal azotemia starting 24 h after SRM administration; the episode resolved over time, and the definitive relationship to SRM administration was not determined. Plasma levels of SRM were higher than CM throughout the initial 24 h, remained variably elevated until 60 h after injection, but failed to sustain presumed therapeutic levels of 400 ng/mL for the full 72 h across all animals in this study. Further investigation is warranted to determine the safety and clinical efficacy of SRM in sheep. Currently, when SRM is used in sheep, we recommend the combination of a preemptive and multimodal analgesia regimen with clinical assessments throughout the postoperative period.