PHARMACOKINETICS AND BIOAVAILABILITY OF TYLVALOSIN AFTER ORAL, INTRAMUSCULAR AND INTRAVENOUS ADMINISTRATION IN TURKEYS
Objective: Tylvalosin, is a new macrolide antibiotic, it is highly effective against a range of important diseases in many different veterinary species specially pigs and poultry. The pharmacokinetics and bioavailability of Tylvalosin were investigated in healthy turkeys.
Methods: Tylvalosin was orally, intramuscularly, and intravenously administrated to turkeys in a single dose of (25 mg/kg b.w.), and the blood samples were analyzed by using a microbiological assay method.
Results: After intravenous injection, the serum concentration-time curves were best described by a two compartment-open model. The distribution and elimination halfâ€“life t 0.5 Î± and t 0.5 Î² were (0.076Â±0.0014 h, 0.788Â±0.107 h), respectively. The volume of distribution Vdss was (1.155Â±0.183 L/kg), with body clearance Cl (B) of (1.489Â±0.143 ml/kg/h). Following oral administration, Tylvalosin was absorbed with t 0.5 ab (0.283Â±0.012 h) and eliminated, with t 0.5 el (5.309Â±0.542 h). The peak serum concentration was (0.637Â±0.018 Âµg/ml) at Tmax of (1.293Â±0.024 h). Following intramuscular administration, Tylvalosin was absorbed with t 0.5 ab (0.076Â±0.003 h) and eliminated with t 0.5 el (0.467Â±0.058 h). The peak serum concentration was (1.446Â±0.121 Âµg/ml) at Tmax of (0.282Â±0.008 h). The systemic bioavailability of Tylvalosin following oral administration was 33.84% and 14.06% after intramuscular administration.
Conclusion: These results indicate that, after oral and intramuscular administration, Tylvalosin was rapidly absorbed and distributed to tissues of turkeys. However, repeated doses are necessary to maintain Tylvalosin serum concentration above the MIC for most susceptible microorganisms.
2. Gigu`ere S. Macrolides, Azalides and Ketolides. In: Antimicrobial therapy in veterinary medicine. 5th ed. S Gigu`ere, JF Prescott, PM Dowling: Wiley-Blackwell, Iowa, USA; 2013. p. 211â€“31.
3. Huang G, Okabe M, Kahar P, Tsunekawa H, Park Y. Optimization of Tylosin feeding rate profile in the production of acetylisovalerylTylosin (AIV) from Tylosin by Streptomyces thermotolerans YN554. J Biosci Bioeng 2001;91:504-8.
4. EMA. Aivlosin, Summary of Product Characteristics. European Medicines Agency; 2004. Available from: http://www.ema.europa.eu/docs/en.GB/document_library/EPAR-Product Information/veterinary/000083/WC500061063 .pdf. [Last accessed on 10 Dec 2012].
5. Zhao Z, Tang X, Zhao X, Zhang M, Zhang W, Hou S, et al. Tylvalosin exhibits anti-inflammatory property and attenuates acute lung injury in different models possibly through suppression of NF-ÎºB activation. Biochem Pharmacol 2014;90:73-87.
6. Cerda RO, Petruccelli M, Piscopo M, Origlia J, Landoni M. Impact of the type of catheter on the absorption of tylvalosin (acetyl valeryl tylosin) administered orally to broiler chickens. J Vet Pharmacol Ther 2009;33:202â€“3.
7. Arret B, Johnoson DP, Kirshaum A. Outline of details of the microbiological assay of ntibiotics: 2nd. revision. J Pharm Sci 1971;60:1489â€“94.
8. Cerda R, Petruccelli MA, Piscopo M, Herrero M, Landoni MF. Pharmacokinetics of acetyl isovaleryl tylosin tartrate (Aivlosin) in 2 w old chicken. Proceedings of the â€˜â€˜Third International Conference on Antimicrobial Agents in Veterinary Medicine; 2006. p. 20.
9. Craig AW, Suh B. Protein binding and the antibacterial effects. Method for the determination of protein binding, In: LORIAN V. Ed. Antibiotics in Laboratory Medicine, rd ed. Baltimore, MD: Williams and Wilkins; 1991. p. 367â€“402.
10. Baggot JD. Some aspects of clinical pharmacokinetics in veterinary medicine. J Vet Pharmacol Ther 1978;1:5â€“18.
11. Snedecor GW. Statistical Methods. 4th ed. Ames, IA: the Iowa State University Press; 1969. p. 91.
12. Baggot JD, Gingerich DA. Pharmacokinetic interpretation of erythromycin and tylosin activity in serum after intravenous administration of a single dose to cows. Res Vet Sci 1976;21:318â€“23.
13. Ji LW, Dong LL, Ji H, Feng XW, Li D, Ding RL, et al. Comparative pharmacokinetics and bioavailability of tylosin tartrate and tylosin phosphate after a single oral and i. v. administration in chickens. J Vet Pharmacol Ther 2014;37:312-5.
14. Galensky RE, Svensson CK. Basic pharmacokinetics, in: Remington JP. Ed. The science and practice of pharmacy. 19th ed. Easton, PA: Mack Publishing Company; 1995. p. 724â€“40.
15. Prats C, El Korchi G, Francesch R, Arboix M, PÃ©rez B. Disposition kinetics of tylosin administered intravenously and intramuscularly to pigs. Res Vet Sci 2002;73:141-4.
16. Kowalski C, RoliÅ„ski Z, ZaÅ„ R, Wawron W. Pharmacokinetics of tylosin in broiler chickens. Pol J Vet Sci 2002;5:127-30.
17. Van Duyn RL, Folkerts TM. Concentrations of tylosin in blood and lung tissue from calves gave single and repeated daily intramuscular doses. VM/SAC Vet Med Small Anim Clin 1979;74:375-7.
18. Stuart AD, Brown TDK, Imrie G, Tasker JB, Mockett APA. Intracellular accumulation and trans-epithelial transport of aivlosin, tylosin and tilmicosin. Pig J 2007;60:26-35.
19. Baggot JD. Distribution of antimicrobial agent in normal and diseased animals. J Am Vet Med Assoc 1980;176:1085â€“90.
20. Riviere JE. Absorption, Distribution, Metabolism and Elimination. In: Veterinary Pharmacology and Therapeutics. 9th ed. Wiley-Blackwell, Ames, IA; 2009. p. 47-74.
21. Abu-Basha A Ehab, Ahmad F Al-Shunnaq, Ronette Gehring. Comparative pharmacokinetics and bioavailability of two tylosin formulations in chickens after oral administration. J Hellenic Veterinary Med Soc 2012;63:159-66.
22. Weisel MK, Powers JD, Powers TE, Baggot JD. A pharmacokinetic analysis of tylosin in the normal dog. Am J Vet Res 1977;38:273-5.
23. Haddad NS, Pedersoli WM, Ravis WR, Fazeli MH, Carson RL. Combined pharmacokinetics of gentamicin in pony mares after a single intravenous and intramuscular administration. Am J Vet Res 1985;46:2004â€“7.
24. Devriese LA, Dutta GN. Effects of erythromycin-inactivating Lactobacillus crop flora on blood levels of erythromycin given orally to chicks. J Vet Pharmacol Ther 1984;7:49â€“53.
25. Dorrestein GM. Formulation and bioavailability problems of drug formulations in birds. J Vet Pharmacol Ther 1992;15:143â€“50.
26. Pommier P, Keita A, Pagot E, Duran O, Cloet PR. Comparison of tylvalosin with Tylosin for the control of subclinical ileitis in swine. Rev Med Vet 2008;159:579-82.
27. Van Leeuwen FXR. Tylosin. In: Toxicological Evaluation of certain veterinary drug residues in food. Thirty-eight meeting of the joint FAO/WHO Expert Committee on Food Additives (JECFA), WHO Food Additives, Series 29, International Programme on Chemical Safety, WHO, Geneva; 1991. p. 139-63.
28. Berkman RN, Richards EA, Van-Duyn RL, Kline RM. The pharmacology of tylosin, a new antibiotic, in chicken. Antimicrob Agents Annu 1961. p. 595-604.
29. Watteyn A, Devreese M, De Baere S, Wyns H, Plessers E, Boyen F, et al. pharmacokinetic and pharmacodynamics properties of gamithromycin in turkey poults with respect to Ornithobacterium rhinotracheale. Poultry Sci 2015;00:1-9.
30. Atef M, El-Gendi AYI, Amer AMM, Kamal GM. Pharmacokinetics assessment of tylosin concomitantly administered with two anticoccidials diclazuril and halofuginone in broiler chickens. Adv Environ Biol 2009;3:210-8.
31. Avci T, Elmas M. Milk and blood pharmacokinetics of tylosin and tilmicosin following parenteral administrations to cows. Sci World J 2014. doi.org/10.1155/2014/869096. [Article in Press].
32. Ziv G, Creveld CV, Ben-Zvi Z, Glickman A, Yagil R. Disposition kinetics of tylosin tartrate administered intravenously and intramuscularly to normal and water-deprived camels. J Vet Pharmacol Ther 1995;18:299-305.
33. Brennan J, Moore G, Poe SE, Zimmermann A, Vessie G, Barnum DA, et al. Efficacy of in-feed tylosin phosphate for the treatment of necrotic enteritis in broiler chickens. Poultry Sci 2001; 80:1451-4.