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oai:ebyu-rdlopen.rawdatalibrary.net:ebyu/111622026-10-18T21:13:15Zopenairedrivercom_ebyu_10000col_ebyu_10001

Plasma and Milk Pharmacokinetics and Estimated Milk Withdrawal Time of Tolfenamic Acid in Lactating SheepCorum, OrhanUney, KamilCoskun, DevranDurna Corum, DuyguCetin, GulElmas, Muammerlactating sheepmilkpharmacokineticstolfenamic acidwithdrawal timeAnimalsAntifibrinolytic AgentsCross-Over StudiesFemaleLactationortho-AminobenzoatesSheepSheep, Domesticnonsteroid antiinflammatory agentanthranilic acid derivativeantifibrinolytic agentanimal experimentarea under the curveArticleblood cell countclinical trialcontrolled studydairy cattledrug blood leveldrug half lifefeverhigh performance liquid chromatographylinear regression analysismastitismaximum plasma concentrationObjective: This study aimed to investigate the plasma and milk pharmacokinetics, as well as the withdrawal time (WT) from milk of tolfenamic acid (2 and 4 mg/kg) following intravenous (IV) administration to eight healthy lactating Akkaraman sheep. Methods: The trial was conducted in two periods in accordance with a crossover pharmacokinetic design. The concentrations of tolfenamic acid in the plasma and milk were determined using high-pressure liquid chromatography and evaluated using non-compartmental analysis. The WT of tolfenamic acid in milk was calculated using the WT 1.4 software. Results: Compared to the 2 mg/kg dose, plasma volume of distribution at steady state (from 0.43 to 0.50 L/kg), terminal elimination half-life (from 2.41 to 4.14 h) and dose-normalized area under the plasma concentration–time curve (AUC0−∞, from 9.46 to 30.11 h µg/mL) increased, whereas total body clearance (from 0.21 to 0.13 L/h/kg) decreased at the 4 mg/kg dose. The peak milk concentration (Cmax) and AUC0−∞ values in milk were 0.26 µg/mL and 0.28 h µg/mL, respectively, for 2 mg/kg, and 0.43 µg/mL and 0.55 h µg/mL, respectively, for 4 mg/kg. Although the dose-normalized Cmax of milk decreased depending on the dose, no difference was observed in dose-normalized AUC0−∞. The AUC0−∞ milk/AUC0−∞ plasma ratio was 0.03 for 2 mg/kg and 0.02 for 4 mg/kg. The WT values calculated for milk at dosages of 2 and 4 mg/kg were 3 and 4 h, respectively. Conclusions: A decrease in plasma elimination and an increase in plasma concentration of tolfenamic acid were observed depending on the dose. Tolfenamic acid lowly passed into sheep's milk at 2 and 4 mg/kg doses. This study may provide valuable information for clinicians’ decision-making processes. © 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.John Wiley and Sons Inc2024Articlehttps://rdlopen.rawdatalibrary.net/r/ebyu/11162https://doi.org/10.1002/vms3.700472053-1095enVeterinary Medicine and Scienceinfo:eu-repo/semantics/openAccessinfo:eu-repo/semantics/articlehttps://ebyu-rdlopen.rawdatalibrary.net/tr/items/ebyu/11162