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

Abstract

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.

Moxidectin is a candidate for use as an in vivo internal standard in pharmacokinetic studies, as demonstrated with use in simultaneous tissue cage and ultrafiltration fluid collection

“…The limited reported use of ultrafiltration probes for pharmacological studies outside laboratory rats gives rise to the possibility of publication bias, the work by Plummer et al ( 23 ), Bidgood and Papich ( 1 ), Messenger et al ( 3 ) and this paper were part of graduate research programs, thus increasing the likelihood of submission of unfavourable results as publication is often a prerequisite for speciality ( 27 , 28 ). Commercially funded work using ultrafiltration probes that did not produce sufficient volumes for analysis may not have been submitted or accepted for publication ( 29 ).…”

“…The early work of Janle stated that subcutaneous probes produced 0.5–1 mL of ultrafiltrate per day. However, Plummer et al ( 23 ) also report low sample volumes (maximum of 1 mL per 4–12 h) from ultrafiltration probes in merino sheep. Additionally, Plummer et al report a high failure and complication rate of UF probes in sheep, similar to our experience in the current study.…”