Bioavailability and pharmacokinetics of oral meloxicam in llamas

Abstract

BackgroundSouth American camelids in the United States have rapidly developed into an important agricultural industry in need of veterinary services. Pain management is challenging in camelids because there are no drugs currently approved by the U.S. Food and Drug Administration for use in these species. Dosage regimens used for many therapeutic drugs have been extrapolated from other ruminants; however, the pharmacokinetics, in camelids, may differ from those of other species. Studies investigating the pharmacokinetics of cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drugs in camelids are deficient in the published literature. Six adult llamas (121- 168 kg) were administered either a 1 mg/kg dose of oral or a 0.5 mg/kg dose of IV meloxicam in a randomized cross-over design with an 11 day washout period between treatments. Plasma samples collected up to 96 hours post-administration were analyzed by high pressure liquid chromatography and mass spectrometry detection (HPLC-MS) followed by non-compartmental pharmacokinetic analysis.ResultsA mean peak plasma concentration (CMAX) of 1.314 μg/mL (Range: 0.826 – 1.776 μg/mL) was recorded at 21.4 hours (Range: 12.0 – 24.0 hours) with a half-life (T ½ λz) of 22.7 hours (Range: 18.0 – 30.8 hours) after oral meloxicam administration. In comparison, a half-life (T ½ λz) of 17.4 hours (Range: 16.2 – 20.7 hours) was demonstrated with IV meloxicam administration. The oral bioavailability (F) of meloxicam (dose normalized) was 76% (Range: 48 – 92%). No adverse effects associated with either treatment modality were observed in the llamas.ConclusionsThe mean bioavailability (F) of oral meloxicam was 76% indicating a high degree of gastrointestinal absorption. Plasma meloxicam concentrations >0.2 μg/mL were maintained for up to 72 h after oral administration; >0.2 μg/mL is considered to be the concentration of meloxicam required for analgesic effects in other species such as the horse. These data suggest that a single dosage of oral meloxicam at 1 mg/kg could potentially maintain therapeutic concentrations in plasma for up to 3 days in adult llamas.

Pharmacokinetics of meloxicam in mature swine after intravenous and oral administration

“…Previous studies have demonstrated excellent bioavailability for meloxicam ranging between 72% and 100% F when administered to horses and ruminants (Calves: Coetzee et al ., ; Goats: Ingvast‐Larsson et al ., ; Horses: Toutain et al ., ; Sheep: Stock et al ., ; Camels: Wasfi et al ., ; Llamas: Kreuder et al ., ). Our study demonstrated oral F at 87% (range 39–350%).…”

“…Our study demonstrated oral F at 87% (range 39–350%). The lower range in F coincides with previous studies conducted in sheep (Stock et al ., ; 40%) and llamas (Kreuder et al ., ; 48%). As there are no other studies assessing bioavailability in sows, it is unclear whether variability in F should be expected in sows or other factors such as feeding regimen or drug formulation influenced this outcome.…”

Effects of Intratesticular and Incisional Local Anesthetic Administration for Castration of Alpacas Anesthetized with Intramuscular Ketamine–Xylazine–Butorphanol

“…Butorphanol and xylazine most likely provided some postoperative analgesia, but this would be short lived. Additional postoperative analgesia in our study was provided by administration of oral meloxicam, which has been shown to have good bioavailability in llamas …”

Impact of oral meloxicam on circulating physiological biomarkers of stress and inflammation in beef steers after long-distance transportation1

“…Plasma concentrations of MEL were determined using high-pressure liquid chromatography (Surveyor MS Pump and Autosampler; Thermo Scientific, San Jose, CA) with mass spectrometry detection (TSQ Quantum Discovery MAX; Thermo Scientific) as previously described (Kreuder et al, 2012). The accuracy of the assay for MEL in bovine plasma was 99 ± 3% of the actual concentration while the coefficient of variation was 5% determined on 4 sets of replicates for each of the following concentrations: 15, 150, and 1,500 ng/mL.…”