Bio-equivalence study of two oral doxycycline formulations (doxycycline kela 75%® and mebcodox 75%®) in broiler Chickens

  • Authors

    • Ashraf El-Komy professor of pharmacology
    • Mohamed Aboubakr
    2020-04-03
    https://doi.org/10.14419/ijpt.v8i1.30477
  • Bioequivalence, Chickens, Doxycycline, oral, Pharmacokinetics.

  • The present study was designed to assess the comparative bio-equivalence of Doxycycline Kela 75%® and Mebcodox 75%® in healthy broiler chickens after oral administration of both products in a dose of 20 mg doxycycline base/kg.b.wt. Twenty four broiler chickens were divided into two groups. The first group was designed to study the pharmacokinetics of Doxycycline Kela 75%®, while the 2nd group was designed to study the pharmacokinetics of Mebcodox 75%®. Each broiler chickens in both groups were orally administered with 20 mg doxycycline base/kg.b.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 The disposition kinetics of Doxycycline Kela 75%® and Mebcodox 75%® following oral administration of 20 mg doxycycline base/kg.b.wt. revealed that the maximum blood concentration [Cmax] were 3.35 and 3.28 μg/ml and attained at [tmax] of 0.97 and 0.99 hours, respectively.

    In conclusion: Mebcodox 75%® is bioequivalent to Doxycycline Kela 75%® since the ratios of Cmax, AUC0-24 and AUC0-∞ (T/R) was 0.97, 0.95 and 0.94 respectively. These are within the bioequivalence acceptance range. Mebcodox 75%® and Doxycycline Kela 75%® are therefore bioequivalent and interchangeable.

     

     

     

  • References

    1. [1] Abd El-Aty, A.M., Goudaha, A., Zhou, H.H. (2004). Pharmacokinetics of doxycycline after administration as a single intravenous bolus and intramuscular doses to non-lactating Egyptian goats. Pharmacological Research 49, 487-491. https://doi.org/10.1016/j.phrs.2003.10.012.

      [2] Anado´n, A., Martinez-Larran˜aga, M.R., Diaz, M.J., Bringas, P., Fernandez, M.C., Fernandez-Cruz, M.L., Iturbe, J. & Martinez, M.A. (1994). Pharmacokinetics of doxycycline in broiler chickens. Avian Pathology, 23: 79–90. https://doi.org/10.1080/03079459408418976.

      [3] Aronson, A.L. (1980). Pharmacotherapeutics of the newer tetracyclines. Journal of the American Veterinary Medical Association, 176: 1061–1068.

      [4] Arret, B.; Johnson, D.P. and Kirshbaum, A. (1971). Outline of details for microbiological assays of antibiotics: second revision. J Pharm Sci. 60(11):1689-1694. https://doi.org/10.1002/jps.2600601122.

      [5] Atef, M., Youssef, S.H.A., EL-Banna, H.A. & EL-Maaz, A.A. (2002). Influence of aflatoxin B1 on the kinetic and disposition, systemic bioavailability and tissue residues of doxycycline in chickens. British Poultry Science, 43: 528–532. https://doi.org/10.1080/0007166022000004435.

      [6] Baggot, J.D. (2001). The physiological Basis of veterinary clinical pharmacology. 1st ed. Blackwell, London. https://doi.org/10.1002/9780470690567.

      [7] Barza, M., Brown, RB. Shanks, C., Gamble, G. & Weinstein, L. (1975). Re1ation berween lipophilicity and pharmacological behaviour of minocyc1ine, doxycyc1ine, tetracyc1ine and oxyretracyc1ine in dogs. Antimicrobial Agents and Chemotherapy, 8, 713-720. https://doi.org/10.1128/AAC.8.6.713.

      [8] Cars, O. & Ryan, M. (1988). Concentrations of doxycyc1ine in musc1e tissue and musc1e tissue fluid. Scandinavian Journal of Infeetious Diseases, Supplementum, 53, 18-27.

      [9] Chen, M.L., V. Shah, R. Patnaik, W. Adams, A. Hussain, D. Conner, M. Mehta, H. alinowski, J. Lazor, S.M. Huang, D. Hare, L. Lesko, D. Sporn and R. Williams, (2001). Bioavailability and bioequivalence: An FDA regulatory overview. Pharmaceutical Res., 18: 1645-1650. https://doi.org/10.1023/A:1013319408893.

      [10] Chow, A.W., Patren, V. & Guze, L.B. (1975). Comparative susceptibility of anaerobic bacteria to minocyc1ine, doxycyc1ine and tetracyc1ine. Antimicrobials Agents and Chemotherapy, 7, 46-49. https://doi.org/10.1128/AAC.7.1.46.

      [11] Craig, W.A. (1998). Pharmacokinetic/pharmacodynamic Croubels, S., Baert, K., De Busser, J. et al. (1998) Residue study of doxycycline and 4-epidoxycycline in pigs medicated via drinking water. The Analyst 123, 2733-2736. https://doi.org/10.1039/a804936j.

      [12] Cunha, B.A., Domenico, P. & Cunha, C.B. (1982). Pharmacodynamics of Doxycycline. Clinical Microbiology & Infection, 6: 270–275. https://doi.org/10.1046/j.1469-0691.2000.00058-2.x.

      [13] Dorrestein, G.M., Welink, J. & Haagsma, N. (1990). Pharmacokinetic differences for doxycycline between racing pigeons (Columba livia) and collared doves (Streptopelia decaveto) and the effect of a salmonellainfection. Deutsche Veterinaar Medizinische Gesellschaft, March: 132–143.

      [14] El-Gendy, A., Atef, M., Amer, A. et al. (2010). Pharmacokinetics and tissue distribution of doxycycline in broiler chickens pretreated with either: Diclazuril or halofuginone. Food and Chemical Toxicology Journal 48, 3209-3214. https://doi.org/10.1016/j.fct.2010.08.024.

      [15] EMEA (2002): Guidelines for the conduct of bioequivalence studies for veterinary medicinal products,1-11[http://www. emea.eu.int/pdfs/vet/ewp/001600en.pdf]2001. Accessed: 30.12.2002.

      [16] EMEA. (2006): The European Agency for Evaluation of Medicinal Products. Questions and Answers on Bioavailability and Bioequivalence Guidance.

      [17] English, RA. (1966). 1X-6-Deoxy-oxytetracyc1ine 1. Some biological properties. Proceedings of the Society for Experimental Biology and Medicine, 122, 1107-1112. https://doi.org/10.3181/00379727-122-31338.

      [18] Fabre, J., Milek, E., Kalefopoulos, P. & Merjer, G. (1971). La cinétique des tétracyc1ines chez I'homme 1. Absorption, digestive et concentrations seriques. Schweizerische Medizinische Wochenschrift, 101, 593-598.

      [19] George, B.A., Fagerberg, D.J., Quarles, C.L. & Fenton, J.M. (1977). Comparison of therapeutic efficacy of doxycycline, chlortetracycline and lincomycin-spectinomycin on E. coli infection of young chickens. Poultry Science, 56, 452-458. https://doi.org/10.3382/ps.0560452.

      [20] Goren, E., De-Jong, W., Doornenbal, P. et al. (1988). Therapeutic efficacy of doxycycline hyclate in experimental Escherichia coli infection in broilers. Veterinary Quarterly 10, 48-52. https://doi.org/10.1080/01652176.1988.9694145.

      [21] Gylstoref, l., Jakoby, J.R. & Gerhermann, H. (1984). Comparative studies on psittacosis control by drugs n. Testing the efficacy of different drugs in various formulations in experimentally infected red

      [22] Hantash, T., Abu-Basha, E., Dergham, A. et al. (2008). Pharmacokinetics and bioequivalence of doxycycline (Providox® and Doxycycline Kela 75% 50 S®) oral powder formulations in chickens. International Journal of Poultry Science 7, 161-164. https://doi.org/10.3923/ijps.2008.161.164.

      [23] Ismail, M.M. & El-Kattan, Y.A. (2004). Disposition kinetics of doxycycline in chickens naturally infected with Mycoplasma gallisepticum. British Poultry Science, 45: 550–556. https://doi.org/10.1080/00071660400001058.

      [24] Jakoby, J.R. (1979). Prevention and treatment of psittacosis with doxycycline (tetracycline) in parrots and parakeets. Berliner und Munchener Tierarztliche Wochenschrijt, 92, 91-95.

      [25] Jha, V., Jayachandran, C., Singh, M. et al. (1989). Pharmacokinetic data on doxycycline and its distribution in different biological fluids in female goats. Veterinary Research Communications 13, 11-16. https://doi.org/10.1007/BF00366847.

      [26] Laczay, P., Semjen, G., Lehel, J. & Nagy, G. (2001). Pharmacokinetics and bioavailability of doxycycline in fasted and nonfasted broiler chickens. Acta Veterinaria Hungarica, 49: 31–37. https://doi.org/10.1556/004.49.2001.1.5.

      [27] Notari, R.E. (1987). Biopharmaceutics and clinical pharmacokinetics an introduction, Principles of pharmacokinetics: dosage regimen, 4th ed., pp. 45—212 (New York, M Dekker) parameters: rationale for antibacterial dosing of mice and men. Clinical Infectious Diseases, 26: 1–12.

      [28] Pashov, D. & Kanelov, I. (1994). Influence of age on pharmacokinetics of doxycycline and of formulation containing tylosin and bromhexine in chickens. Proceedings of the 6th EAVPT Congress, Edinburgh, 64—65.

      [29] Perez, B.T., Rosado, R.I. & Sa´ Nchez, M.L. (2006). Vacunas contra Mycoplasma gallisepticum. REDVET Revista electro´nica de Veterinaria, VII,1—22 http://redalyc.uaemex. mx/src/inicio/ArtPdfRed.jsp?iCve=63612653034 Organizacio´n.

      [30] Prats, G., Elkorchi, G., Giralt, M. et al. (2005). PK and PK/PD of doxycycline in drinking water after therapeutic use in pigs. Journal of Veterinary Pharmacology and Therapeutics 28, 525-530. https://doi.org/10.1111/j.1365-2885.2005.00700.x.

      [31] Prescott, J.F., Baggot, J.D. & Walker, R.D. (2000). Antimicrobial Therapy in Veterinary Medicine, 3th ed., pp. 275—289 (Ames, USA, Iowa State University Press).

      [32] Riond, J., Riviere, J. (1990). Pharmacokinetics and metabolic inertness of doxycycline in young pigs. American Journal of Veterinary Research 51, 1271-1275.

      [33] Riviere, J.E. & Spoo, J.W. (2003). Tetracycline antibiotics, in: ADAMS, H.R. (Ed.) Farmacologı´a y Terape´utica Veterinaria, 2th ed., pp. 834—835 (Zaragoza, Espan˜a, Acribia).

      [34] Santos, M.D.F., Vermeersch, H. & Remon, J.P. (1996) Validation of a high-performance liquid chromatographic method for the determination of doxycycline in turkey plasma. Journal of Chromatography, 682: 301–308. https://doi.org/10.1016/0378-4347(96)00076-X.

      [35] Saux, M.C., Mosser, J., Pontagnier, H. & Leng, B. (1981). Pharmacokinetics of doxycycline polyphosphate (PPD), hydrochloride (CHD) and base (DB). European Journal of Drug Metabolism and Pharmacokinetics, 6, 3-10. https://doi.org/10.1007/BF03189510.

      [36] Schach Von Wittenau, M. & Delahunt, C.S. (1966). The distribution oftetracyclines in tissues of dogs after repeated oral administration. Journal of Pharmacology and Experimental Therapeutics, 152, 164-169.

      [37] Shaw, D.H. & Rubin, S.T. (1986). Pharmacologic activity of doxycycline. Journal of the American Veterinary Medical Association, 189: 808–10.

      [38] Stipkovits, L., Marca, J., Sisquella, L. & Navarrete, E. (2004). Administracio´n de un inmunoterape´utico oral para incrementar la eficacia del tratamiento con tetraciclinas en pollos infectados experimentalmente con Mycoplasma gallisepticun. Available: http://www.manolofolio.co.uk/ calier/articulos/aves/avesnov04.pdf.

      [39] Takahashi, I., Yoshida, T. (1989). Antimycoplasmal activities of ofloxacin and commonly used antimicrobial agents on Mycoplasma gallisepticum. The Japanese Journal of Antibiotics 42, 1166-1172.

      [40] Toutain PL, Del Castillo JRE, Bousquet-Mélou A. (2002). The pharmacokinetic-pharmacodynamic approach to a rational dosage regimen for antibiotics. Res Vet Sci, 73:105–14. https://doi.org/10.1016/S0034-5288(02)00039-5.

      [41] Toutain, P.L. and A. Bousquet-Melou, (2004). Bioavailability and its assessment. J. Pharmacol. Therap., 27: 455-466. https://doi.org/10.1111/j.1365-2885.2004.00604.x.

      [42] Vargas, D., Gutie´rrez, L., Jua´rez, I., Gonza´lez, F. & Sumano, H. (2008). Pharmacokinetics of an injectable long—action parenteral formulation of doxycycline hyclate in goats. American Journal of Veterinary Research, 69: 1085–1090. https://doi.org/10.2460/ajvr.69.8.1085.

      [43] Walker, R.D., Stein, G.E., Hauptman, J.G. and Macdonald, K.H. (1992): Pharmacokinetics evaluation of enrofloxacin administered orally to healthy dogs. Am. J. Vet. Res., 53: 2315-2319.

      [44] Wiluamson, G.M. (1968). The in vitro activity of vibramycin (doxycycline). Chemotherapy, Supplementum, 13, 1-6. https://doi.org/10.1159/000220576.

      [45] Yoshida, M., Kubota, D., Yonezawa, S. et al. (1971). Transfer of dietary spiramycin into the eggs and its residue in the liver of laying hen. The Japanese Journal of Antibiotics 8, 103-110. https://doi.org/10.2141/jpsa.8.103.

      [46] Yoshida, M., Kubota, d., Yonezawa, S. et al. (1973). Transfer of dietary doxycycline into the eggs and its residue in the liver of laying hen. The Japanese Journal of Antibiotics 10, 29-36. https://doi.org/10.2141/jpsa.10.29.

      [47] Yoshimura, H., Osawa, N., Rasa, F. et al. (1991). Residues of doxycycline and oxytetracycline in eggs after medication via drinking water to laying hens. Fo`od Additives and contaminants 8, 65-69 https://doi.org/10.1080/02652039109373956.

      [48] Zhang N, Gu X, Ye X, Wu X, Zhang B, Zhang L, Shen X, Jiang H, Ding H. (2016) The PK/PD Interactions of Doxycycline against Mycoplasma gallisepticum. Front Microbiol. 7:653. https://doi.org/10.3389/fmicb.2016.00653.

  • Downloads

  • How to Cite

    El-Komy, A., & Aboubakr, M. (2020). Bio-equivalence study of two oral doxycycline formulations (doxycycline kela 75%® and mebcodox 75%®) in broiler Chickens. International Journal of Pharmacology and Toxicology, 8(1), 54-59. https://doi.org/10.14419/ijpt.v8i1.30477