Pharmacokinetics of meloxicam, carprofen, and tolfenamic acid after intramuscular and oral administration in Japanese quails (<i>Coturnix coturnix japonica</i>)

et al. 2022

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The aim of this study was to determine the pharmacokinetics and bioavailability of carprofen in sheep following single intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations of a parenteral formulation at a dose of 4 mg/ kg. A total of eight sheep were used for the investigation. The study comprised four periods, according to a crossover design with a 21-day washout period between treatments. Plasma concentrations of carprofen were measured using HPLC-UV.Pharmacokinetic parameters were estimated by non-compartmental model analysis. Following IV administration, t 1/2ʎz , Cl T , and V dss were 43.36 h, 1.98 ml/h/kg, and 121.36 ml/kg, respectively. The C max(obs) was 26.57 mg/ml for the IM, 23.76 mg/ml for the SC, and 15.90 mg/ml for the PO. The bioavailability following IM, SC, and PO administrations was 75.47%, 82.00%, and 62.51%, respectively. Plasma creatine kinase activity increased significantly at 3, 6, and 12 h following IM administration of carprofen. Despite differences in plasma concentrations and bioavailability among administration routes, carprofen at 4 mg/kg dose may provide the plasma concentration (>1.5 μg/ml) needed for analgesic effect during 144 h in all routes. However, because of the slow absorption rate after SC and PO routes, the IV route may be preferred primarily for the rapid onset in the analgesic and anti-inflammatory effect of carprofen in sheep. Despite the favorable kinetics, the muscle damage caused by IM injection limits use of carprofen via IM route.

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics and bioavailability of carprofen in sheep

Coşkun

et al. 2022

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“…The C max and T max of meloxicam were 1.95 μg/ml and 0.5 h, respectively, in Nile Tilapia ( Oreochromis niloticus ) after the IM administration at the dose of 1 mg/kg (Fredholm et al, 2016). After oral administration of meloxicam at a dose of 1 mg/kg, C max and T max were 0.83–3.10 μg/ml and 6.5–21.4 h in mammals (Coetzee et al, 2009; Fredholm et al, 2013), and 0.1–10.84 μg/ml and 0.5–13.2 h in avian species (Turk et al, 2021), respectively. C max and T max of meloxicam in animal species differed due to differences in drug formulations and nutritional habits, as well as physiological and anatomical differences.…”

Section: Discussionmentioning

confidence: 99%

“…The plasma concentrations of meloxicam were assayed using the HPLC‐UV (Shimadzu, Tokyo, Japan) according to the previous method (Tekeli et al, 2020; Turk et al, 2021). Briefly, the 200 μl of methanol containing 0.1% formic acid was added to a 100 μl of fish plasma sample followed vortexed for 40 s and centrifuged at 12,000 g for 15 min.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics and bioavailability of meloxicam in rainbow trout (Oncorhynchus mykiss) broodstock following intravascular, intramuscular, and oral administrations

Terzi̇

et al. 2021

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Pain causes behavioral, autonomic, and neuroendocrine changes, resulting in animal welfare degradation (Steagall et al., 2021). It has been found that fish have nociceptors that transmit painful stimuli and are quite similar to those found in mammals (Chatigny et al., 2018;Sneddon, 2012). Noxious stimulation causes adverse behavioral and physiological changes in various fish species (Sneddon, 2003(Sneddon, , 2012. Therefore, analgesics are recommended for painful and inflammatory conditions, such as trauma-related injuries, cutaneous ulceration, and surgical operations, in fish (Greene et al., 2020;Weber, 2011).Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for pain management in veterinary medicine. In clinical studies in fish, NSAIDs did not cause significant side effects, while opioids caused adverse effects on the cardiovascular and respiratory systems (Chatigny et al., 2018). NSAIDs show analgesic, antipyretic, and anti-inflammatory properties by inhibiting the cyclooxygenase (COX) enzymes responsible for prostaglandin synthesis from arachidonic acid (Sneddon, 2012). COX-1 is constitutively expressed throughout the body and is of particular importance in maintaining normal physiological functions, and COX-2 is the inducible form, expression of which is enhanced by growth factors, cytokines, and other inflammatory stimuli (Hawkey, 2001). Rainbow

“…The plasma concentration of carprofen was analyzed using the HPLC–UV system (Shimadzu) by the previously reported method (Uney et al, 2021; Turk, Tekeli, Corum, et al, 2021). Briefly, plasma samples were precipitated by adding 300 μl of acetate buffer (1 M, pH: 2.8) to 200 μl of plasma samples followed by vortex for 45 s and centrifugation at 10,000 × g for 12 min.…”

Section: Methodsmentioning

confidence: 99%

“…It shows analgesic, antipyretic, and anti‐inflammatory properties by inhibiting the cyclooxygenase enzyme (COX) responsible for prostaglandin synthesis from arachidonic acid (Mitchell, 2005). NSAIDs with the COX‐1/COX‐2 selectivity ratio of >1 for inhibitory concentration (IC) 50 are considered more potent in inhibiting COX‐2 (Hunter et al, 2015; Turk, Tekeli, Corum, et al, 2021). Since the COX‐1/COX‐2 ratio of carprofen is >1 in sheep (5.3–6.3), it has inhibition, especially on COX‐2 (Cheng et al, 2003; Mitchell, 2005).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of carprofen following single and repeated intravenous administrations of different doses in sheep

Coşkun

et al. 2022

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The aim of this study was to determine the pharmacokinetics of carprofen following single and repeated intravenous (IV) administrations at 1.4 and 4 mg/kg doses in sheep. The study was carried out on twelve sheep in two experiments as single‐ and multiple‐dose pharmacokinetics. In experiment 1, carprofen was administered via IV at single doses of 1.4 (n = 6) and 4 mg/kg (n = 6) in a randomized parallel design. In experiment 2, the same dose groups in experiment 1 following the 21‐day washout period received intravenously carprofen every 24 h for 5 days. Plasma concentrations were measured using high‐performance liquid chromatography–UV and analyzed by a two‐compartment open model. After the single administration of 1.4 mg/kg dose, the t1/2α, t1/2el, MRT, ClT, Vdss, and AUC were 0.62 h, 27.57 h, 38.78 h, 2.72 ml/h/kg, 105.26 ml/kg, and 515.12 h*μg/ml, respectively. Carprofen at a single dose of 4 mg/kg showed prolonged t1/2el and MRT, and increased Vdss. On day 5 after the repeated administration of the 1.4 mg/kg dose, the t1/2α, t1/2el, MRT, ClT, Vdss, and AUC were 1.12 h, 57.48 h, 82.18 h, 0.55 ml/h/kg, 45.43 ml/kg, and 2532 h*μg/ml, respectively. Carprofen at a repeated dose of 4 mg/kg showed increased ClT and Vdss and decreased AUC/dose. Although the long t1/2ʎz in single and multiple IV dose studies suggest the possibility of its effective use, the IV route may not be practical in sheep. Therefore, oral and subcutaneous routes of carprofen in sheep would be more valuable in clinical settings.