Comparative pharmacokinetics and absolute bioavailabilities of two enrofloxacin generic preparations after single intracrop bolus administrations to broiler chickens

  • Authors

    • Nasser Ehmeza
    • Abdelrazzag Elmajdoub
    • Abubakr El-Mahmoudy Benha University
    2016-06-25
    https://doi.org/10.14419/ijpt.v4i2.6248
  • Bioavailability, Bioequivalence, Broiler, Chicken, Enrofloxacin, Intracrop, Intravenous, Pharmacokinetics.

  • Abstract

    The pharmacokinetics and absolute bioavailabilities of two generics of enrofloxacin (ENRO) 10% oral solution formulation at a dose of 10 mg/Kg body weight were compared after single intracrop (i.c.) bolus administrations in reference to single intravenous (i.v.) standard ENRO administration in broilers using a randomized parallel design. The two tested formulations were Enrol® (Medmac®, Amman, Jordan) as ENRO-A and Syvaquinol® (Syva®, Leon, Spain) as ENRO-B 10% oral solutions. An HPLC assay using pure ENRO base as a standard was used to measure concentrations of ENRO from the selected sources in plasma collected at predetermined time points up to 24 hours. The pharmacokinetic analysis of the C-T data was performed using non-compartmental analysis based on statistical moment theory with the help of computerized WinNonlin program (Version 5.3, Pharsight® Corporation, St. Louis, USA). The maximum plasma concentrations (Cmax) for ENRO-A and ENRO-B were 1.61 ± 0.203 and 1.79 ± 0.283 μg/mL, respectively, attained at time to peak (Tmax) of 2 h. Elimination half-lives (t1/2β) were 8.391 ± 0.312 and 8.458 ± 0.906 h, respectively. While areas under plasma concentration-time curves (AUC0-∞), and systemic bioavailabilities (F) were 12.744 ± 2.951 and 14.354 ± 2.85 mg.h/L; and 78.96 ± 6.728 and 88.94 ± 10.89 % for ENRO-A and ENRO-B, respectively. It could be concluded that despite the superior pharmacokinetic profile of ENRO-B over ENRO-A, however, both generics were within the FDA and EMA bioequivalence acceptance range of 80%–125% and thus can be used as interchangeable therapeutic agents in chickens.


  • References

    1. [1] Abd El-Aziz M, Aziz M, Soliman F & Afify N 1997, Pharmacokinetic evaluation of enrofloxacin in chickens. British poultry science 38, 164-168. http://dx.doi.org/10.1080/00071669708417963.

      [2] Altreuther P 1987, [Data on chemistry and toxicology of Baytril]. Veterinaer-Medizinische Nachrichten (Germany, FR).

      [3] Anadon A, Martinez Larranaga MR, Diaz MJ, Fernandez- cruze ML, Martinez MA, Bringas P, Fernandez MC & Fernandez R 1995, Pharmacokinetics and residues of enrofloxacin in chickens. American journal of Veterinary Research 56, 501-506.

      [4] Anderson AD, Nelson JM, Rossiter S & Angulo FJ 2003, Public health consequences of use of antimicrobial agents in food animals in the United States. Microbial Drug Resistance 9, 373-379. http://dx.doi.org/10.1089/107662903322762815.

      [5] Baggot JD 1977, Principles of drug disposition in domestic animals: the basis of veterinary clinical pharmacology: WB Saunders.

      [6] Ball P 2000, Quinolone generations: natural history or natural selection? Journal of Antimicrobial Chemotherapy 46, 17-24. http://dx.doi.org/10.1093/oxfordjournals.jac.a020889.

      [7] Birkett DJ 2003, Generics-equal or not? Australian Prescriber 26, 85-86. http://dx.doi.org/10.18773/austprescr.2003.063.

      [8] Bugyei K, Black WD & McEwen S 1999, Pharmacokinetics of enrofloxacin given by the oral, intravenous and intramuscular routes in broiler chickens. Canadian Journal of Veterinary Research 63, 193-200.

      [9] EMA CfMPfHU 2010, Guideline on the investigation of bioequivalence. European Medicines Agency (EMA), London.

      [10] FDA 2005, Food and Drug Administration final decision of the Commissioner. Docket no. 2000n-1571. Withdrawal of approval of the new animal drug application for enrofloxacin in poultry.

      [11] FDA 2015, Bioavailability and bioequivalence requirements, Subpart B-Procedures for Determining the Bioavailability or Bioequivalence of Drug Products. In: CFR - Code of Federal Regulations Title 21. USA.

      [12] Garcia Ovando H, Gorla N, Luders C, Poloni G, Errecalde C, Prieto G & Puelles I 1999, Comparative pharmacokinetics of enrofloxacin and ciprofloxacin in chickens. Journal of Veterinary Pharmacology and Therapeutics 22, 209-212. http://dx.doi.org/10.1046/j.1365-2885.1999.00211.x.

      [13] Gberindyer FA, Noel Wannang N & Akwuobu CA 2010, Comparative pharmacokinetics/pharmacodynamic modeling on three brands of 10% enrofloxacin oral formulations in broiler chickens. International Journal of Poultry Science 9, 273-277. http://dx.doi.org/10.3923/ijps.2010.273.277.

      [14] Gellert M, Mizuuchi K, O'Dea MH, Itoh T & Tomizawa J-I 1977, Nalidixic acid resistance: a second genetic character involved in DNA gyrase activity. Proceedings of the National Academy of Sciences 74, 4772-4776. http://dx.doi.org/10.1073/pnas.74.11.4772.

      [15] Gibaldi M & Perriere D 2007, Pharmacokinetics In: Noncompartmental Analysis Based on Statistical Moment Theory, 2nd ed. New York, USA: Informa Healthcare. p 409-417.

      [16] Heitzman RJ 1997, Enrofloxacin In: Identity. Berkshire, United Kingdom. p 31-44.

      [17] Jakubowski P, Jaroszewski J, Grabowski T, Markiewicz W & Maslanka T 2010, Determination of enrofloxacin in chicken plasma by high performance liquid chromatography for pharmacokinetic studies. Acta veterinaria 60, 563-572. http://dx.doi.org/10.2298/AVB1006563J.

      [18] Khan MK, Khan MF, Mustafa G & Sualah M 2012, Comparison of High-Pressure Liquid Chromatography and microbiological assay for determination of ciprofloxacin tablets in human plasma employed in bioequivalence and pharmacokinetics study. Pak J Pharm Sci 25, 81-88.

      [19] Knoll U, Glünder G & Kietzmann M 1999, Comparative study of the plasma pharmacokinetics and tissue concentrations of danofloxacin and enrofloxacin in broiler chikens. Journal of Veterinary Pharmacology and Therapeutics 22, 239-246. http://dx.doi.org/10.1046/j.1365-2885.1999.00217.x.

      [20] Küng K, RIOND JL & Wanner M 1993, Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after intravenous and oral administration of enrofloxacin in dogs. Journal of Veterinary Pharmacology and Therapeutics 16, 462-468.

      [21] Lesher GY, Froelich EJ, Gruett MD, Bailey JH & Brundage RP 1962, 1, 8-Naphthyridine derivatives. A new class of chemotherapeutic agents. Journal of Medicinal Chemistry 5, 1063-1065. http://dx.doi.org/10.1021/jm01240a021.

      [22] Mekala P, Jagadeeswaran A, Arivuchelvan A, Senthilkumar P, Nanjappan K & Krishnamurthy TG 2014, Pharmacokinetics of Enrofloxacin after Single Intravenous and Oral Bolus Administration in Broiler Chicken. International Journal of Advanced Veterinary Science and Technology 3, pp. 99-105.

      [23] Midha KK & McKay G 2009, Bioequivalence; its history, practice, and future. The AAPS journal 11, 664-670. http://dx.doi.org/10.1208/s12248-009-9142-z.

      [24] Nielsen P & Gyrd-Hansen N 1997, Bioavailability of enrofloxacin after oral administration to fed and fasted pigs. Pharmacology & toxicology 80, 246-250. http://dx.doi.org/10.1111/j.1600-0773.1997.tb01967.x.

      [25] Posyniak A, Zmudzki J, Niedzielska J & Biernacki B 2001, Bioequivalence study of two formulations of enrofloxacin following oral administration in chickens. Bulletin of the Veterinary Research Institute in Pulawy 45, 353-358.

      [26] Rao G, Ramesh S, Ahmad A, Tripathi H, Sharma L & Malik J 2002, Disposition kinetics of enrofloxacin and ciprofloxacin following intravenous administration of enrofloxacin in goats. Small Ruminant Research 44, 9-15. http://dx.doi.org/10.1016/S0921-4488(02)00003-2.

      [27] Sumano H & Ocampo L 1995, Compositional Analysis Surveillance of Eleven Brands of Enrofloxacin Including Baytril® for Veterinary Use. Journal of Veterinary Medicine Series A 42, 669-673. http://dx.doi.org/10.1111/j.1439-0442.1995.tb00421.x.

      [28] Sumano L, Gomez R, Gracia M & Ruiz-Ramirez L 1994, The use of ciprofloxacin in veterinary proprietary products of enrofloxacin. Veterinary and human toxicology 36, 476-477.

      [29] Van Bambeke F, Michot JM, Van Eldere J & Tulkens PM 2005, Quinolones in 2005: an update. Clinical Microbiology and infection 11, 256-280. http://dx.doi.org/10.1111/j.1469-0691.2005.01131.x.

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  • How to Cite

    Ehmeza, N., Elmajdoub, A., & El-Mahmoudy, A. (2016). Comparative pharmacokinetics and absolute bioavailabilities of two enrofloxacin generic preparations after single intracrop bolus administrations to broiler chickens. International Journal of Pharmacology and Toxicology, 4(2), 115-122. https://doi.org/10.14419/ijpt.v4i2.6248

    Received date: 2016-05-15

    Accepted date: 2016-06-16

    Published date: 2016-06-25