Plasma and Milk Pharmacokinetics and Estimated Milk Withdrawal Time of Tolfenamic Acid in Lactating Sheep

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dc.authoridUney, Kamil/0000-0002-8674-4873
dc.authoridCoskun, Devran/0000-0003-1151-1861
dc.authoridCorum, Orhan/0000-0003-3168-2510
dc.contributor.authorCorum, Orhan
dc.contributor.authorUney, Kamil
dc.contributor.authorCoskun, Devran
dc.contributor.authorDurna Corum, Duygu
dc.contributor.authorCetin, Gul
dc.contributor.authorElmas, Muammer
dc.date.accessioned2024-12-24T19:24:22Z
dc.date.available2024-12-24T19:24:22Z
dc.date.issued2024
dc.departmentSiirt Üniversitesi
dc.description.abstractObjective: 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 (AUC(0-infinity), from 9.46 to 30.11 h mu g/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 (C-max) and AUC(0-infinity) values in milk were 0.26 mu g/mL and 0.28 h mu g/mL, respectively, for 2 mg/kg, and 0.43 mu g/mL and 0.55 h mu g/mL, respectively, for 4 mg/kg. Although the dose-normalized C-max of milk decreased depending on the dose, no difference was observed in dose-normalized AUC(0-infinity). The AUC(0-infinity milk)/AUC(0-infinity 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.
dc.description.sponsorshipCoordination of Scientific Research Projects, University of Selcuk, Turkiye [22401010]
dc.description.sponsorshipThis work was supported by the Coordination of Scientific Research Projects, University of Selcuk, Turkiye (Project No: 22401010).
dc.identifier.doi10.1002/vms3.70047
dc.identifier.issn2053-1095
dc.identifier.issue6
dc.identifier.pmid39321188
dc.identifier.scopus2-s2.0-85204912909
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1002/vms3.70047
dc.identifier.urihttps://hdl.handle.net/20.500.12604/5950
dc.identifier.volume10
dc.identifier.wosWOS:001319963500001
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherWiley
dc.relation.ispartofVeterinary Medicine and Science
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_20241222
dc.subjectlactating sheep
dc.subjectmilk
dc.subjectpharmacokinetics
dc.subjecttolfenamic acid
dc.subjectwithdrawal time
dc.titlePlasma and Milk Pharmacokinetics and Estimated Milk Withdrawal Time of Tolfenamic Acid in Lactating Sheep
dc.typeArticle

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