DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20201103

Bio-equivalence study of two tilmicosin phosphate formulations (Micotil 300® and Cozina 300®) in broiler chickens

Ashraf Elkomy, Mohamed Aboubakr

Abstract


Background: The present study was designed to assess the comparative bio-equivalence of Micotil 300® and Cozina 300® in healthy broiler chickens after oral administration of both products in a dose of 15 mg tilmicosin base/kg body wt.

Methods: Twenty four broiler chickens were divided equally into two groups (12 chickens for each group). The first group was designed to study the pharmacokinetics of Micotil 300®, while the 2nd group was designed to study the pharmacokinetics of Cozina 300®. Each broiler chicken in both groups was orally administered with 15 mg tilmicosin/kg body wt. Blood samples were obtained from the wing vein and collected immediately before and at 0.08, 0.16, 0.25, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours after a single oral administration.

Results: The disposition kinetics of Micotil 300® and Cozina 300® following oral administration of 15 mg tilmicosin/kg body wt revealed that the maximum blood concentration [Cmax] were 1.73 and 1.67 μg/ml and attained at [tmax] of 2.01 and 2.04 hours, respectively.

Conclusions: Cozina 300® is bioequivalent to Micotil 300® since the ratios of Cmax, AUC0-24 andAUC0-∞ (T/R) were 0.96, 0.93 and 0.91 respectively. These are within the bio-equivalence acceptance range. Micotil 300® and Cozina 300® are therefore bioequivalent and interchangeable.


Keywords


Pharmacokinetics, Chickens, Tilmicosin

Full Text:

PDF

References


Prescott, JF. Macrolides and pleuromyilins. Antimicrobial Therapy in Veterinary Medicine, 3rd edn. Iowa State University Press, Ames, IA: 2000: 229-262.

Moore GM, Basson RP, Tonkinson LV. Clinical field trials with tilmicosin in feed for the control of naturally acquired pneumonia caused by Actinobacillus pleuropneumoniae and Pasteurella multocida in swine. Am J Vet Res. 1996;57:224-8.

Hoar BR, Jelinski MD, Ribble CS, Janzen ED, Johnson JC. A comparison of the clinical field efficacy and safety of florfenicol and tilmicosin for the treatment of undifferentiated bovine respiratory disease of cattle in western Canada. Candian Vet J. 1998;39:161-6.

Christodoulopoulos G, Warnick LD, Papaioannou N, Fthenakis GC. Tilmicosin administration to young lambs with respiratory infection:safety and efficacy considerations. J Vet Pharmacol Therap. 2002;25:393-7.

Jordan FT, Horrocks BK. The minimum inhibitory concentration of tilmicosin and tylosin for Mycoplasma gallisepticum and Mycoplasma synoviae and a comparison of their efficacy in the control of Mycoplasma gallisepticum infection in broiler chicks. Avian Diseases. 1996;40:326-34.

Kempf I, Reeve-Johnson L, Gesbert F, Guittet M. Efficacy of tilmicosin in the control of experimental Mycoplasma gallisepticum infection in chickens. Avian Dis. 1997;41:802-7.

EMEA. The European Agency for the Evaluation of Medicinal Products Veterinary Medicines Evaluation Unit. Committee for veterinary medicinal products. Tilmicosin (extension to chicken), summary report 2. Available at: http://www.emea.eu.int/pdfs/vet/mrls/ 039098en.pdf. Accessed on 3 June 2019.

Ziv G, Shem-Tov M, Glickman A, Winkler M, Saran, A. Tilmicosin antibacterial activity and pharmacokinetics in cows. J Vet Pharmacol Therap. 1995;18(5):340-5.

Chen ML, Shah V, Patnaik R, Adams W, Hussain A, Conner D, Mehta M, alinowski H, Lazor J, Huang SM, Hare D, Lesko L, Sporn D, Williams R. Bioavailability and Bio-equivalence:An FDA regulatory overview. Pharm Res. 2001;18:1645-50.

Toutain PL, Bousquet-Melou A. Bioavailability and its assessment. J Pharmacol Therap. 2004;27:455-66.

Arret B, Johnson DP, Kirshbaum A. Outline of details for microbiological assays of antibiotics:second revision. J Pharm Sci. 1971;60(11):1689-94.

Baggot JD. The physiological Basis of veterinary clinical pharmacology. 1st ed. Blackwell, London. 2011.

EMEA. Guidelines for the conduct of Bio-equivalence studies for veterinary medicinal products,1-11. Available at: http://www.emea.eu. int/pdfs/vet/ewp/001600en.pdf. Accessed on 30 December 2002.

EMEA. The European Agency for Evaluation of Medicinal Products. Questions and Answers on Bioavailability and Bio-equivalence Guidance. 2006.

Main BW, Means JR, Rinkema LE, Smith WC, Sarazan RD. Cardiovascular effects of the macrolide antibiotic tilmicosin, administered alone and in combination with propranolol or dobutamine, in conscious unrestrained dogs. J Vet Pharmacol Therap. 1996;19:225-232.

Papich MG, Riviere JE. Chloramphenicol and derivatives, macrolides, lincosamides and miscellaneous antimicrobials. Veterinary Pharmacology and Therapeutics, 8th edn. Iowa State Press, Ames, IA: 2001: 880-881.

Abu-Basha EA, Idkaidek NM, Al-Shunnaq A F. Pharmacokinetics of tilmicosin (Provitil powder and pulmotil liquid AC) oral formulations in chickens. Vet Res Comm. 2007;31:477-85.

Shen J, Li C, Jiang H, Zhang S, Guo P, Ding S, Li X. Pharmacokinetics of tilmicosin after oral administration in swine. Am J Vet Res. 2005;66:1071-1074.

Abu-Basha EA, Al-Shunnaq AF, Gehring R. Com-parative pharmacokinetics and bioavailability of two tylosin formu-lations in chickens after oral administration. J Hellenic Vet Med Soc. 2012;63:159-66.

Soliman AM, Sedek M. Pharmacokinetics and Tissue Residues of Tylosin in Broiler Chickens. Pharmacol Pharma. 2016;7:36-42.

Dimitrova D, Кatsarov V, Dimitrov D, Tsoneva, D. Pharmacokinetics of tilmicosin after oral application of Pulmotil G 200 - premix in pigs. Agricultural Sci Tech. 2011;3;318-22.

El-Hewaity‏ M. Effect of three anticoccidials on pharmacokinetics of tilmicosin in broiler chickens.‏ Int J Pharmacol Toxicol. 2016;4(2):150-3.‏

Zhang N, Ye X, Wu Y, Huang Z, Gu X, Cai Q, et al. Determination of the Mutant Selection Window and Evaluation of the Killing of Mycoplasma gallisepticum by Danofloxacin, Doxycycline, Tilmicosin, Tylvalosin and Valnemulin. PLoS One. 2017;12(1):e0169134.

Rowlan M, Tozer TN. Clinical Pharmacology: Concepts and Applications. 2nd ed. Philadelphia: Lea & Febiger; 1989: 479-483.

U.S. Food and Drug Administration. Guidance for industry:bioavailability and Bio-equivalence studies for orally administered drug products. U.S. Food and Drug Administration, Washington, DC: 2003.