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

Christine Plummer,Dominique Van der Saag,Peter J. White,Benjamin Kimble,Merran Govendir

doi:10.3390/ani11092484

Christine Plummer, Dominique Van der Saag + Show 3 more

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https://doi.org/10.3390/ani11092484

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Abstract

Simple SummaryMeloxicam is an effective non-steroidal anti-inflammatory drug (NSAID) suitable for ameliorating pain in sheep. Pain caused by husbandry procedures and other inflammatory conditions in sheep can persist for an extended time beyond the duration of action of currently available formulations of NSAIDs. This study investigates a novel sustained-release formulation of meloxicam to determine its potential for extended pain alleviation. Compared to a conventional formulation of meloxicam, the sustained-release formulation provided extended half-life making it a suitable candidate for providing extended pain relief.This study is a preliminary investigation describing the pharmacokinetic profile of a novel subcutaneous sustained-release meloxicam formulation (SRMF) in sheep. Six merino ewe hoggets (41.5 ± 4.6 kg) were treated with a novel subcutaneous SRMF at 2 mg/kg bodyweight (BW). Blood samples were collected at t = 0, 2, 4, 6, 8, 10, 12, 24, 48, 96, 144, 168, 192, and 336 h following treatment, and interstitial (ISF) fluid samples were collected at periods of 8 to 12 h, 12 to 24 h, 24 to 48 h, 48 to 52 h, and 92 to 96 h following treatment. High-pressure liquid chromatography (HPLC) analysis with ultraviolet detection was utilised to determine the concentration of meloxicam in plasma and ISF. The SRMF exhibited the following mean (±SD) pharmacokinetic indices: Cmax of 1.58 μg/mL (±0.82 μg/mL) at a Tmax of 10.0 h (±1.79 h), and half life (t1/2) of 31.4 h (±13.17 h) in sheep plasma. Interstitial fluid samples were collected from three of the six sheep, with a decrease in meloxicam concentration exhibited over 52 h. This study demonstrates a variable extended t1/2, a delayed Tmax, and a lower Cmax of the SRMF, as compared to that of a conventional meloxicam formulation (CMF) in sheep, as previously referenced (t1/2: 14.28 h; Tmax: 5 h; Cmax: 15.94 μg/mL). Further research to determine the clinical efficacy and safety of the SRMF in sheep is warranted.

Highlights

Meloxicam is an enolic acid that belongs to the oxicam class of non-steroidal antiinflammatory drugs (NSAIDs) [1]
Plasma sustained-release meloxicam formulation (SRMF) concentrations detected in each sheep over 96 h and over time are presented in Figures 1 and 2, respectively
The plasma concentrations of the SRMF used in this study provided an extended t1/2 of 31.40 h comparative to the conventional meloxicam formulation (CMF) t1/2 of 14.28 h, when both were administered at

Summary

Introduction

Meloxicam is an enolic acid that belongs to the oxicam class of non-steroidal antiinflammatory drugs (NSAIDs) [1]. Meloxicam possesses a higher therapeutic index than other NSAIDs due to its analgesic, anti-inflammatory, and antipyretic properties [2,3]. 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]

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