Plasma and Milk Pharmacokinetics and Estimated Milk Withdrawal Time of Tolfenamic Acid in Lactating Sheep
ABSTRACT Objective 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 perio...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-11-01
|
| Series: | Veterinary Medicine and Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/vms3.70047 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832593433679626240 |
|---|---|
| author | Orhan Corum Kamil Uney Devran Coskun Duygu Durna Corum Gul Cetin Muammer Elmas |
| author_facet | Orhan Corum Kamil Uney Devran Coskun Duygu Durna Corum Gul Cetin Muammer Elmas |
| author_sort | Orhan Corum |
| collection | DOAJ |
| description | ABSTRACT Objective 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. |
| format | Article |
| id | doaj-art-ba2fd7f68150448784abb50e4353fdab |
| institution | Kabale University |
| issn | 2053-1095 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Veterinary Medicine and Science |
| spelling | doaj-art-ba2fd7f68150448784abb50e4353fdab2025-01-20T17:16:44ZengWileyVeterinary Medicine and Science2053-10952024-11-01106n/an/a10.1002/vms3.70047Plasma and Milk Pharmacokinetics and Estimated Milk Withdrawal Time of Tolfenamic Acid in Lactating SheepOrhan Corum0Kamil Uney1Devran Coskun2Duygu Durna Corum3Gul Cetin4Muammer Elmas5Department of Pharmacology and Toxicology Faculty of Veterinary Medicine University of Hatay Mustafa Kemal Antakya Hatay TürkiyeDepartment of Pharmacology and Toxicology Faculty of Veterinary Medicine University of Selcuk Konya TürkiyeDepartment of Pharmacology and Toxicology Faculty of Veterinary Medicine University of Siirt Siirt TürkiyeDepartment of Pharmacology and Toxicology Faculty of Veterinary Medicine University of Hatay Mustafa Kemal Antakya Hatay TürkiyeDepartment of Pharmacology Faculty of Pharmacy University of Erzincan Binali Yıldırım Erzincan TürkiyeDepartment of Pharmacology and Toxicology Faculty of Veterinary Medicine University of Selcuk Konya TürkiyeABSTRACT Objective 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.https://doi.org/10.1002/vms3.70047lactating sheepmilkpharmacokineticstolfenamic acidwithdrawal time |
| spellingShingle | Orhan Corum Kamil Uney Devran Coskun Duygu Durna Corum Gul Cetin Muammer Elmas Plasma and Milk Pharmacokinetics and Estimated Milk Withdrawal Time of Tolfenamic Acid in Lactating Sheep Veterinary Medicine and Science lactating sheep milk pharmacokinetics tolfenamic acid withdrawal time |
| title | Plasma and Milk Pharmacokinetics and Estimated Milk Withdrawal Time of Tolfenamic Acid in Lactating Sheep |
| title_full | Plasma and Milk Pharmacokinetics and Estimated Milk Withdrawal Time of Tolfenamic Acid in Lactating Sheep |
| title_fullStr | Plasma and Milk Pharmacokinetics and Estimated Milk Withdrawal Time of Tolfenamic Acid in Lactating Sheep |
| title_full_unstemmed | Plasma and Milk Pharmacokinetics and Estimated Milk Withdrawal Time of Tolfenamic Acid in Lactating Sheep |
| title_short | Plasma and Milk Pharmacokinetics and Estimated Milk Withdrawal Time of Tolfenamic Acid in Lactating Sheep |
| title_sort | plasma and milk pharmacokinetics and estimated milk withdrawal time of tolfenamic acid in lactating sheep |
| topic | lactating sheep milk pharmacokinetics tolfenamic acid withdrawal time |
| url | https://doi.org/10.1002/vms3.70047 |
| work_keys_str_mv | AT orhancorum plasmaandmilkpharmacokineticsandestimatedmilkwithdrawaltimeoftolfenamicacidinlactatingsheep AT kamiluney plasmaandmilkpharmacokineticsandestimatedmilkwithdrawaltimeoftolfenamicacidinlactatingsheep AT devrancoskun plasmaandmilkpharmacokineticsandestimatedmilkwithdrawaltimeoftolfenamicacidinlactatingsheep AT duygudurnacorum plasmaandmilkpharmacokineticsandestimatedmilkwithdrawaltimeoftolfenamicacidinlactatingsheep AT gulcetin plasmaandmilkpharmacokineticsandestimatedmilkwithdrawaltimeoftolfenamicacidinlactatingsheep AT muammerelmas plasmaandmilkpharmacokineticsandestimatedmilkwithdrawaltimeoftolfenamicacidinlactatingsheep |