Araştırma Makalesi
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Pharmacokinetics of Meloxicam Following Repeated Intravenous Administrations in Sheep

Yıl 2025, Cilt: 18 Sayı: 1, 82 - 87

Öz

The purpose of this study was to investigate the pharmacokinetics of meloxicam following repeated intravenous injection in sheep. Five male merino sheep were used in the study. Meloxicam was administered intravenously to sheep at 0.5 mg/kg once daily for 5 days. Meloxicam analysis from plasma samples was performed by high-pressure liquid chromatography. Non-compartmental analysis was used to establish the pharmacokinetic parameters. Following the first dose of meloxicam, the values for the plasma concentration at the first sampling time (C0.08), area under the plasma concentration-time (AUC0-24), elimination half-life (t1/2ʎz), total body clearance (ClT), and volume of distribution at steady state (Vdss), were 2.53 µg/mL, 12.30 hour*µg/mL, 8.97 hour, 0.03 L/hour/kg, and 0.40 L/kg, respectively. Compared to the first dose, AUC0-24 and C0.08 increased, ClT and Vdss decreased after the last dose administration. Following the first and final administration, the t1/2ʎz values were similar. The accumulation levels of R1 and R2 were 2.48 and 2.81, respectively. In conclusion, repeated administration of meloxicam in sheep caused pharmacokinetic changes and accumulation. Therefore, the safety and therapeutic effect of meloxicam after repeated administration in sheep should be established.

Etik Beyan

Araştırma Selçuk Üniversitesi Deney Hayvanları Yerel Etik Kurulu tarafından 26.03.2015 tarihinde ve 2015/03 numaralı oturumda görüşülmüş olup, 2015/30 numaralı kararınca etik kurul izni alınmıştır.

Destekleyen Kurum

Bu araştırma herhangi bir kurum ve kuruluş tarafından desteklenmemektedir.

Kaynakça

  • Adawaren, E. O., Mukandiwa, L., Chipangura, J., Wolter, K., & Naidoo, V. (2019). Percentage of faecal excretion of meloxicam in the Cape vultures (Gyps corprotheres). Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, 215, 41–46. https://doi.org/10.1016/j.cbpc.2018.10.001
  • Anonymous 2024. https://troylab.com.au/wp-content/uploads/2023/06/TRO3939_ILIUM-MELOXICAM-20_AU_PIS_082B_D2.pdf. [Access Date: 04.01.2025].
  • Carpenter, J. W., Pollock, C. G., Koch, D. E., & Hunter, R. P. (2009). Single and multiple-dose pharmacokinetics of meloxicam after oral administration to the rabbit (Oryctolagus cuniculus). Journal of Zoo and Wildlife Medicine, 40(4), 601–606. https://doi.org/10.1638/2007-0115.1
  • Colburn, W. A. (1983). Estimating the accumulation of drugs. Journal of Pharmaceutical Sciences, 72, 833–834. https://doi.org/10.1002/jps.2600720734
  • Cordeiro, A. R. R. D. A., Bezerra, T. K. A., & Madruga, M. S. (2022). Valuation of goat and sheep by-products: Challenges and opportu- nities for their use. Animals, 12(23), 3277. https://doi.org/10.1002/jps.2600720734.
  • Corum, O., Corum, D. D., Er, A., & Uney, K. (2019). Pharmacokinetics of cefquinome after single and repeated subcutaneous administrations in sheep. . Journal of Veterinary Pharmacology and Therapeutics, 42(6), 647–653. https://doi.org/10.1111/jvp.12750.
  • Corum, O., Corum, D. D., Er, A., Yildiz, R., & Uney, K. (2018). Pharmacokinetics and bioavailability of tolfenamic acid in sheep. Journal of Veterinary Pharmacology and Therapeutics, 41(6), 871–877. https://doi.org/10.1111/jvp.12702.
  • Corum, O., Coskun, D., Durna Corum, D., Ider, M., Yildiz, R., Ok, M., & Uney, K. (2022ba). Pharmacokinetics of carprofen following single and repeated intravenous administrations of different doses in sheep. Journal of Veterinary Pharmacology and Therapeutics, 45(5), 481–487. https://doi.org/10.1111/jvp.13079.
  • Corum, O., Terzi, E., Durna Corum, D., & Uney, K. (2022ab). Pharmacokinetics and bioavailability of meloxicam in rainbow trout (Oncorhynchus mykiss) broodstock following intravascular, intramuscular, and oral administrations. Journal of Veterinary Pharmacology and Therapeutics, 45(2), 213–219. https://doi.org/10.1111/jvp.13031.
  • Coskun, D., Corum, O., Durna Corum, D., Cetin, G., Irmak, M., Ceyhan, H. R., & Uney, K. (2023b). Age‐related changes in the pharmacokinetics of meloxicam after intravenous administration in sheep. Journal of Veterinary Pharmacology and Therapeutics, 46(5), 326–331. https://doi.org/10.1111/jvp.13404.
  • Coskun, D., Corum, O., Corum, D. D., & Uney, K. (2023). Pharmacokinetics and bioavailability of meloxicam in Pekin ducks following intravenous, intramuscular and oral administration. Veterinary Anaesthesia and Analgesia, 50(6), 477–484. https://doi.org/10.1016/j.vaa.2023.07.007.
  • CVMP. (2006). Committee for medicinal products for veterinary use: meloxi- cam summary report (7). EMEA/CVMP/152255/2006-FİNAL. https://www.ema.europa.eu/en/documents/mrl-report/meloxicam-extrapolation-rabbits-goats-summary-report-7-committee- veterinary-medicinal-products_en.pdf. [Access Date: 04.01.2025].
  • Depenbrock, S., Urbano, T., Ziegler, J., Wetzlich, S., Clapham, M. O., & Tell, L. A. (2021). Pharmacokinetic parameters and tissue withdrawal intervals for sheep administered multiple oral doses of meloxicam. Animals, 11(10), 2797. https://doi.org/10.3390/ani11102797.
  • Gates, B. J., Nguyen, T. T., Setter, S. M., & Davies, N. M. (2005). Meloxicam: A reappraisal of pharmacokinetics, efficacy and safety. Expert Opinion on Pharmacotherapy, 6(12), 2117–2140. https://doi.org/10.1517/14656566.6.12.2117.
  • Gungor, H., Corum, O., Durna Corum, D., Kumru, A. S., Yilmaz, G., Coskun, D., Coskun A & Uney, K. (2024). Pharmacokinetics of meloxicam following intravenous administration at different doses in sheep. Journal of Veterinary Pharmacology and Therapeutics, 47(3), 202–207. https://doi.org/10.1111/jvp.13422.
  • Jeunesse, E. C., Bargues, I. A., Toutain, C. E., Lacroix, M. Z., Letellier, I. M., Giraudel, J. M., & Toutain, P. L. (2011). Paw inflammation model in dogs for preclinical pharmacokinetic/pharmacodynamic investigations of nonsteroidal anti-inflammatory drugs. Journal of Pharmacology and Experimental Therapeutic, 338(2), 548–558. https://doi.org/10.1124/jpet.110.178350.
  • Li, L., Li, X., Xu, L., Sheng, Y., Huang, J., & Zheng, Q. (2013). Systematic evaluation of dose accumulation studies in clinical pharmacokinetics. Current Drug Metabolism, 14, 605–615. https://doi.org/10.2174/13892002113149990002.
  • Li, M., Wang, Y. S., Elwell-Cuddy, T., Baynes, R. E., Tell, L. A., Davis, J. L., Maunsell, P. F., Riviere, J. E., & Lin, Z. (2021). Physiological parameter values for physiologically based pharmacokinetic models in food-producing animals. Part III: Sheep and goat. Journal of Veterinary Pharmacology and Therapeutics, 44(4), 456–477. https://doi.org/10.1111/jvp.12938.
  • Lindemann, D. M., Carpenter, J. W., & KuKanich, B. (2016). Pharmacokinetics of a single dose of oral and subcutaneous meloxicam in Caribbean flamingos (Phoenicopterus ruber ruber). Journal of Avian Medicine and Surgery, 30(1), 14–22. https://doi.org/10.1647/2014-065.
  • Sakai, J. B. (2009). Practical pharmacology for the pharmacy technician. Philadelphia, PA: Lippincott Williams & Wilkins, 1st ed., pp. 27–40.
  • Sim, T. (2016). Meloxicam product approved for sheep in Australia after world-first tri-lateral review. Sheepcentral.com. https://www.sheep central.com/meloxicam-product-approved-for-sheep-in-australia- after-world-first-tri-lateral-review/ [Access Date: 04.01.2025].
  • Sladky, K. K. (2023). Treatment of pain in reptiles. Veterinary Clinics: Exotic Animal Practice, 26(1), 43–64.
  • Stock, M. L., Coetzee, J. F., KuKanich, B., & Smith, B. I. (2013). Pharmacokinetics of intravenously and orally administered meloxicam in sheep. American Journal of Veterinary Research, 74(5), 779–783. https://doi.org/10.2460/ajvr.74.5.779.
  • Tekeli, I. O., Turk, E., Durna Corum, D., Corum, O., & Uney, K. (2020). Effect of castration procedure on the pharmacokinetics of meloxicam in goat kids. Journal of Veterinary Pharmacology and Therapeutics, 43(5), 429–434. https://doi.org/10.1111/jvp.12872.
  • Toutain, P. L., Reymond, N., Laroute, V., Garcia, P., Popot, M. A., Bonnaire, Y., Hirsch, A., & Narbe, R. (2004). Pharmacokinetics of meloxicam in plasma and urine of horses. American Journal of Veterinary Research, 65(11), 1542–1547. https://doi.org/10.2460/ajvr.2004.65.1542.
  • Toutain, P. L., & Cester, C. C. (2004). Pharmacokinetic-pharmacodynamic relationships and dose response to meloxicam in horses with induced arthritis in the right carpal joint. American Journal of Veterinary Research, 65(11), 1533–1541. https://doi.org/10.2460/ajvr.2004.65.1533.
  • Turk, E., Tekeli, I. O., Durna Corum, D., Corum, O., Sakin, F., & Uney, K. (2021). Pharmacokinetics of tolfenamic acid after different administration routes in geese (Anser cygnoides). Journal of Veterinary Pharmacology and Therapeutics, 44(3), 381–387. https://doi.org/10.1111/jvp.12956.
  • Woodland, A. N., Van der Saag, D., Kimble, B., White, P. J., Govendir, M., & Lomax, S. (2019). Plasma pharmacokinetic profile and efficacy of meloxicam administered subcutaneously and intramuscularly to sheep. Plos one, 14(4), e0215842. https://doi.org/10.1371/journal.pone.0215842.

Koyunlarda Meloksikamın Tekrarlanan İntravenöz Uygulamasını Takiben Farmakokinetiği

Yıl 2025, Cilt: 18 Sayı: 1, 82 - 87

Öz

Bu çalışmanın amacı, koyunlarda meloksikamın tekrarlanan intravenöz enjeksiyonunu takiben farmakokinetiğini belirlemektir. Araştırma 5 baş Merinos ırkı erkek koyun üzerinde gerçekleştirildi. Meloksikam koyunlara günde bir defa 5 gün boyunca 0.5 mg/kg dozunda intravenöz olarak uygulandı. Plazma örneklerinden meloksikam analizi yüksek basınçlı sıvı kromatografisi ile gerçekleştirildi. Farmakokinetik parametreleri kompartmansız analiz ile belirlendi. Meloksikamın ilk dozundan sonra ilk örnekleme zamanındaki plazma konsantrasyonu (C0.08), plazma konsantrasyon-zaman eğrisi altında kalan alan (AUC0-24), eliminasyon yarı ömrü (t1/2ʎz), toplam vücut klirensi (ClT) ve kararlı durum dağılım hacmi (Vdss) değerleri, sırasıyla 2.53 µg/mL, 12.30 saat*µg/mL, 8.97 saat, 0.03 L/saat/kg ve 0.40 L/kg olarak bulundu. İlk doza göre, son doz uygulamasından sonra AUC0-24 ve C0.08 artarken, ClT ve Vdss azaldı. İlk ve son uygulamayı takiben t1/2ʎz değerleri benzerdi. R1 ve R2 birikim seviyeleri sırasıyla 2.48 ve 2.81 idi. Sonuç olarak, koyunlarda meloksikamın tekrarlanan uygulanması farmakokinetik değişikliklere ve birikime neden oldu. Bu nedenle, koyunlarda tekrarlanan uygulamadan sonra meloksikamın güvenliği ve terapötik etkisi belirlenmelidir.

Kaynakça

  • Adawaren, E. O., Mukandiwa, L., Chipangura, J., Wolter, K., & Naidoo, V. (2019). Percentage of faecal excretion of meloxicam in the Cape vultures (Gyps corprotheres). Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, 215, 41–46. https://doi.org/10.1016/j.cbpc.2018.10.001
  • Anonymous 2024. https://troylab.com.au/wp-content/uploads/2023/06/TRO3939_ILIUM-MELOXICAM-20_AU_PIS_082B_D2.pdf. [Access Date: 04.01.2025].
  • Carpenter, J. W., Pollock, C. G., Koch, D. E., & Hunter, R. P. (2009). Single and multiple-dose pharmacokinetics of meloxicam after oral administration to the rabbit (Oryctolagus cuniculus). Journal of Zoo and Wildlife Medicine, 40(4), 601–606. https://doi.org/10.1638/2007-0115.1
  • Colburn, W. A. (1983). Estimating the accumulation of drugs. Journal of Pharmaceutical Sciences, 72, 833–834. https://doi.org/10.1002/jps.2600720734
  • Cordeiro, A. R. R. D. A., Bezerra, T. K. A., & Madruga, M. S. (2022). Valuation of goat and sheep by-products: Challenges and opportu- nities for their use. Animals, 12(23), 3277. https://doi.org/10.1002/jps.2600720734.
  • Corum, O., Corum, D. D., Er, A., & Uney, K. (2019). Pharmacokinetics of cefquinome after single and repeated subcutaneous administrations in sheep. . Journal of Veterinary Pharmacology and Therapeutics, 42(6), 647–653. https://doi.org/10.1111/jvp.12750.
  • Corum, O., Corum, D. D., Er, A., Yildiz, R., & Uney, K. (2018). Pharmacokinetics and bioavailability of tolfenamic acid in sheep. Journal of Veterinary Pharmacology and Therapeutics, 41(6), 871–877. https://doi.org/10.1111/jvp.12702.
  • Corum, O., Coskun, D., Durna Corum, D., Ider, M., Yildiz, R., Ok, M., & Uney, K. (2022ba). Pharmacokinetics of carprofen following single and repeated intravenous administrations of different doses in sheep. Journal of Veterinary Pharmacology and Therapeutics, 45(5), 481–487. https://doi.org/10.1111/jvp.13079.
  • Corum, O., Terzi, E., Durna Corum, D., & Uney, K. (2022ab). Pharmacokinetics and bioavailability of meloxicam in rainbow trout (Oncorhynchus mykiss) broodstock following intravascular, intramuscular, and oral administrations. Journal of Veterinary Pharmacology and Therapeutics, 45(2), 213–219. https://doi.org/10.1111/jvp.13031.
  • Coskun, D., Corum, O., Durna Corum, D., Cetin, G., Irmak, M., Ceyhan, H. R., & Uney, K. (2023b). Age‐related changes in the pharmacokinetics of meloxicam after intravenous administration in sheep. Journal of Veterinary Pharmacology and Therapeutics, 46(5), 326–331. https://doi.org/10.1111/jvp.13404.
  • Coskun, D., Corum, O., Corum, D. D., & Uney, K. (2023). Pharmacokinetics and bioavailability of meloxicam in Pekin ducks following intravenous, intramuscular and oral administration. Veterinary Anaesthesia and Analgesia, 50(6), 477–484. https://doi.org/10.1016/j.vaa.2023.07.007.
  • CVMP. (2006). Committee for medicinal products for veterinary use: meloxi- cam summary report (7). EMEA/CVMP/152255/2006-FİNAL. https://www.ema.europa.eu/en/documents/mrl-report/meloxicam-extrapolation-rabbits-goats-summary-report-7-committee- veterinary-medicinal-products_en.pdf. [Access Date: 04.01.2025].
  • Depenbrock, S., Urbano, T., Ziegler, J., Wetzlich, S., Clapham, M. O., & Tell, L. A. (2021). Pharmacokinetic parameters and tissue withdrawal intervals for sheep administered multiple oral doses of meloxicam. Animals, 11(10), 2797. https://doi.org/10.3390/ani11102797.
  • Gates, B. J., Nguyen, T. T., Setter, S. M., & Davies, N. M. (2005). Meloxicam: A reappraisal of pharmacokinetics, efficacy and safety. Expert Opinion on Pharmacotherapy, 6(12), 2117–2140. https://doi.org/10.1517/14656566.6.12.2117.
  • Gungor, H., Corum, O., Durna Corum, D., Kumru, A. S., Yilmaz, G., Coskun, D., Coskun A & Uney, K. (2024). Pharmacokinetics of meloxicam following intravenous administration at different doses in sheep. Journal of Veterinary Pharmacology and Therapeutics, 47(3), 202–207. https://doi.org/10.1111/jvp.13422.
  • Jeunesse, E. C., Bargues, I. A., Toutain, C. E., Lacroix, M. Z., Letellier, I. M., Giraudel, J. M., & Toutain, P. L. (2011). Paw inflammation model in dogs for preclinical pharmacokinetic/pharmacodynamic investigations of nonsteroidal anti-inflammatory drugs. Journal of Pharmacology and Experimental Therapeutic, 338(2), 548–558. https://doi.org/10.1124/jpet.110.178350.
  • Li, L., Li, X., Xu, L., Sheng, Y., Huang, J., & Zheng, Q. (2013). Systematic evaluation of dose accumulation studies in clinical pharmacokinetics. Current Drug Metabolism, 14, 605–615. https://doi.org/10.2174/13892002113149990002.
  • Li, M., Wang, Y. S., Elwell-Cuddy, T., Baynes, R. E., Tell, L. A., Davis, J. L., Maunsell, P. F., Riviere, J. E., & Lin, Z. (2021). Physiological parameter values for physiologically based pharmacokinetic models in food-producing animals. Part III: Sheep and goat. Journal of Veterinary Pharmacology and Therapeutics, 44(4), 456–477. https://doi.org/10.1111/jvp.12938.
  • Lindemann, D. M., Carpenter, J. W., & KuKanich, B. (2016). Pharmacokinetics of a single dose of oral and subcutaneous meloxicam in Caribbean flamingos (Phoenicopterus ruber ruber). Journal of Avian Medicine and Surgery, 30(1), 14–22. https://doi.org/10.1647/2014-065.
  • Sakai, J. B. (2009). Practical pharmacology for the pharmacy technician. Philadelphia, PA: Lippincott Williams & Wilkins, 1st ed., pp. 27–40.
  • Sim, T. (2016). Meloxicam product approved for sheep in Australia after world-first tri-lateral review. Sheepcentral.com. https://www.sheep central.com/meloxicam-product-approved-for-sheep-in-australia- after-world-first-tri-lateral-review/ [Access Date: 04.01.2025].
  • Sladky, K. K. (2023). Treatment of pain in reptiles. Veterinary Clinics: Exotic Animal Practice, 26(1), 43–64.
  • Stock, M. L., Coetzee, J. F., KuKanich, B., & Smith, B. I. (2013). Pharmacokinetics of intravenously and orally administered meloxicam in sheep. American Journal of Veterinary Research, 74(5), 779–783. https://doi.org/10.2460/ajvr.74.5.779.
  • Tekeli, I. O., Turk, E., Durna Corum, D., Corum, O., & Uney, K. (2020). Effect of castration procedure on the pharmacokinetics of meloxicam in goat kids. Journal of Veterinary Pharmacology and Therapeutics, 43(5), 429–434. https://doi.org/10.1111/jvp.12872.
  • Toutain, P. L., Reymond, N., Laroute, V., Garcia, P., Popot, M. A., Bonnaire, Y., Hirsch, A., & Narbe, R. (2004). Pharmacokinetics of meloxicam in plasma and urine of horses. American Journal of Veterinary Research, 65(11), 1542–1547. https://doi.org/10.2460/ajvr.2004.65.1542.
  • Toutain, P. L., & Cester, C. C. (2004). Pharmacokinetic-pharmacodynamic relationships and dose response to meloxicam in horses with induced arthritis in the right carpal joint. American Journal of Veterinary Research, 65(11), 1533–1541. https://doi.org/10.2460/ajvr.2004.65.1533.
  • Turk, E., Tekeli, I. O., Durna Corum, D., Corum, O., Sakin, F., & Uney, K. (2021). Pharmacokinetics of tolfenamic acid after different administration routes in geese (Anser cygnoides). Journal of Veterinary Pharmacology and Therapeutics, 44(3), 381–387. https://doi.org/10.1111/jvp.12956.
  • Woodland, A. N., Van der Saag, D., Kimble, B., White, P. J., Govendir, M., & Lomax, S. (2019). Plasma pharmacokinetic profile and efficacy of meloxicam administered subcutaneously and intramuscularly to sheep. Plos one, 14(4), e0215842. https://doi.org/10.1371/journal.pone.0215842.
Toplam 28 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Veteriner Farmakoloji
Bölüm ARAŞTIRMA MAKALESİ
Yazarlar

Orhan Çorum 0000-0003-3168-2510

Duygu Durna Çorum 0000-0003-1567-991X

Kamil Üney 0000-0002-8674-4873

Ayşe Er 0000-0002-6900-0055

Muammer Elmas 0000-0001-9059-7151

Erken Görünüm Tarihi 13 Mart 2025
Yayımlanma Tarihi
Gönderilme Tarihi 11 Ocak 2025
Kabul Tarihi 1 Mart 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 18 Sayı: 1

Kaynak Göster

APA Çorum, O., Durna Çorum, D., Üney, K., Er, A., vd. (2025). Pharmacokinetics of Meloxicam Following Repeated Intravenous Administrations in Sheep. Kocatepe Veterinary Journal, 18(1), 82-87.
AMA Çorum O, Durna Çorum D, Üney K, Er A, Elmas M. Pharmacokinetics of Meloxicam Following Repeated Intravenous Administrations in Sheep. kvj. Mart 2025;18(1):82-87.
Chicago Çorum, Orhan, Duygu Durna Çorum, Kamil Üney, Ayşe Er, ve Muammer Elmas. “Pharmacokinetics of Meloxicam Following Repeated Intravenous Administrations in Sheep”. Kocatepe Veterinary Journal 18, sy. 1 (Mart 2025): 82-87.
EndNote Çorum O, Durna Çorum D, Üney K, Er A, Elmas M (01 Mart 2025) Pharmacokinetics of Meloxicam Following Repeated Intravenous Administrations in Sheep. Kocatepe Veterinary Journal 18 1 82–87.
IEEE O. Çorum, D. Durna Çorum, K. Üney, A. Er, ve M. Elmas, “Pharmacokinetics of Meloxicam Following Repeated Intravenous Administrations in Sheep”, kvj, c. 18, sy. 1, ss. 82–87, 2025.
ISNAD Çorum, Orhan vd. “Pharmacokinetics of Meloxicam Following Repeated Intravenous Administrations in Sheep”. Kocatepe Veterinary Journal 18/1 (Mart 2025), 82-87.
JAMA Çorum O, Durna Çorum D, Üney K, Er A, Elmas M. Pharmacokinetics of Meloxicam Following Repeated Intravenous Administrations in Sheep. kvj. 2025;18:82–87.
MLA Çorum, Orhan vd. “Pharmacokinetics of Meloxicam Following Repeated Intravenous Administrations in Sheep”. Kocatepe Veterinary Journal, c. 18, sy. 1, 2025, ss. 82-87.
Vancouver Çorum O, Durna Çorum D, Üney K, Er A, Elmas M. Pharmacokinetics of Meloxicam Following Repeated Intravenous Administrations in Sheep. kvj. 2025;18(1):82-7.

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