Bioequivalence Study of Two Oral Doxycycline Formulations (Doxysol^® and Doxymed^®) in Healthy Broiler Chickens

Ahmed M. Soliman^1*, Mohamed Aboubakr², Mohamed El-Hewaity³

¹Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
²Department of Pharmacology, Faculty of Veterinary Medicine, Benha University, Qaliobiya, Egypt.
³Department of Pharmacology, Faculty of Veterinary Medicine, University of Sadat City, Minoufiya, Egypt.

DOI: 10.4236/pp.2015.61001                

Abstract

Aims: The present study was designed to assess the comparative bio-equivalence of Doxysol^® and Doxymed^® in healthy broiler chickens after oral administration of both products in a dose of 20 mg doxycycline/kg.b.wt. Materials and Methods: Twenty broiler chickens were divided into two groups. The first group was designed to study the pharmacokinetics of Doxysol, while the 2nd group was designed to study the pharmacokinetics of Doxymed. Each broiler chickens in both groups were injected intravenously with 20 mg doxycycline/kg.b.wt. Blood samples were obtained from the wing vein and collected immediately before and at 5, 15, 30 minute, 1, 2, 4, 6, 8, 12 and 24 hours after a single intravenous or oral administration. Results: Doxycycline in both products obeyed a two compartments open model following I.V. injection in a dose of 20 mg/kg.b.wt. The disposition kinetics of Doxysol^® and Doxymed^® following oral administration of 20 mg doxycycline base/kg.b.wt. revealed that the maximum blood concentration [C_max.] were 4.70 and 4.65 μg/ml and attained at [t_max.] of 1.30 and 1.40 hours, respectively. Doxycycline in Doxysol^® and Doxymed^® was eliminated with half-lives [t_0.5(β)] equal to 1.98 and 2.31 hours, respectively. The mean systemic bioavailability of doxycycline in Doxysol^® and Doxymed^® after oral administration in healthy chickens was 92.57 and 88.21%, respectively. Conclusion: Doxymed^® is bioequivalent to Doxysol^® since C_{max test}/C_{max reference} and AUC_test/AUC_reference ratios were 99% and 90%, respectively.

Keywords

Bioequivalence, Doxycycline, Broiler Chickens, Pharmacokinetics

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Jha, V.K., Jayachandran, C., Singh, M.K. and Singh, S.D. (1989) Pharmacokinetic Data on Doxycycline and Its Distribution in Different Biological Fluids in Female Goats. Veterinary Research Communications, 13, 11-16. http://dx.doi.org/10.1007/BF00366847
[2]	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. http://dx.doi.org/10.1111/j.1365-2885.2005.00700.x
[3]	Riond, J.L. and Riviere, J.E. (1990) Pharmacokinetics and Metabolic Inertness of Doxycycline in Young Pigs. American Journal of Veterinary Research, 51, 1271-1275.
[4]	Goren, E., De-Jong, W., Doornenbal, P., et al. (1988) Therapeutic Efficacy of Doxycycline Hyclate in Experimental Escherichia coli Infection in Broilers. Vet Q, 10, 48-52. http://dx.doi.org/10.1080/01652176.1988.9694145
[5]	Croubels, S., Baert, K., De Busser, J. and De Backer, P. (1998) Residue Study of Doxycycline and 4-Epidoxycycline in Pigs Medicated via Drinking Water. Analyst, 123, 2733-2736. http://dx.doi.org/10.1039/a804936j
[6]	Abd El-Aty, A.M., Goudah, A. and 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.
[7]	Chen, M.L., Shah, V., Patnaik, R., et al. (2001) Bioavailability and Bioequivalence: An FDA Regulatory Overview, Pharmaceutical Research, 18, 1645-1650. http://dx.doi.org/10.1023/A:1013319408893
[8]	Toutain, P.L. and Bousquet-Melou, A. (2004) Bioavailabilty and Its Assessment. Journal of Veterinary Pharmacology and Therapeutics, 27, 455-466. http://dx.doi.org/10.1111/j.1365-2885.2004.00604.x
[9]	Arret, B., Johnson, D. and Kirshbaum, A. (1971) Outline of Details for Microbiological Assay of Antibiotics. Journal of Pharmaceutical Sciences, 60, 1689-1694. http://dx.doi.org/10.1002/jps.2600601122
[10]	Baggot, J. (1978) Some Aspects of Clinical Pharmacokinetics in Veterinary Medicine. Journal of Veterinary Pharmacology and Therapeutics, 1, 5-18. http://dx.doi.org/10.1111/j.1365-2885.1978.tb00300.x
[11]	Yoshida, M., Kubota, D., Yonezawa, S., Nakamura, H., Azechi, H. and Terakado, N. (1971) Transfer of Dietary Spiramycin into the Eggs and Its Residue in the Liver of Laying Hen. Japanese Journal of Antibiotics, 8, 103-110.
[12]	Yoshida, M., Kubota, D., Yonezawa, S., Nakamura, H., Azechi, H. and Terakado, N. (1973) Transfer of Dietary Doxycycline into the Eggs and Its Residue in the Liver of Laying Hen. Japanese Journal of Antibiotics, 10, 29-36.
[13]	Roadaut, B., Moretain, J.P. and Boisseau, J. (1987) Excretion of Oxytetracycline in Eggs after Medication of Laying Hens. Food Additives and Contaminants, 4, 297-307. http://dx.doi.org/10.1080/02652038709373639
[14]	Roadaut, B. and Moretain, J.P. (1990) Residues of Macrolide Antibiotics in Eggs Following Medication of Laying Hens. British Poultry Science, 31, 661-675. http://dx.doi.org/10.1080/00071669008417297
[15]	Yoshimura, H., Osawa, N., Rasa, F.S.C., Hermawati, D., Werdiningsih, S., Isriyanthi, N.M.R. and Sugimori, T. (1991) Residues of Doxycycline and Oxytetracycline in Eggs after Medication via Drinking Water to Laying Hens. Food Additives and Contaminants, 8, 65-69. http://dx.doi.org/10.1080/02652039109373956
[16]	Omija, B., Mitema, E.S. and Maitho, T.E. (1994) Oxytetracycline Residue Levels in Chicken Eggs after Oral Administration of Medicated Drinking Water to Laying Chickens. Food Additives and Contaminants, 11, 641-647. http://dx.doi.org/10.1080/02652039409374265
[17]	Anadon, A., Martinez-Larranaga, M.R., Diaz, M.J., Bringas, P., Fernandez, M.C., Fernandez-Cruz, M.L., et al. (1994) Pharmacokinetics of Doxycycline in Broiler Chickens. Avian Pathology, 23, 79-90. http://dx.doi.org/10.1080/03079459408418976
[18]	Laczay, P., Semjen, G., Lehel, J. and Nagy, G. (2001) Pharmacokinetics and Bioavailability of Doxycycline in Fasted and Non-Fasted Broiler Chickens. Acta Veterinaria Hungarica, 49, 31-37. http://dx.doi.org/10.1556/AVet.49.2001.1.5
[19]	Ismail, M.M. and El-Kattan, Y.A. (2004) Disposition Kinetics of Doxycycline in Chickens Naturally Infected with Mycoplasma gallisepticum. British Poultry Science, 45, 550-556. http://dx.doi.org/10.1080/00071660400001058
[20]	Hantash, T.M., Abu-Basha, E.A., Roussan, D.A. and Abudabos, A.M. (2008) Pharmacokinetics and Bioequivalence of Doxycycline (Providox® and Doxyveto 50 S®) Oral Powder Formulations in Chickens. International Journal of Poultry Science, 7, 161-164. http://dx.doi.org/10.3923/ijps.2008.161.164
[21]	El-Gendy, A.Y., Atef, M., Amer, A.M. and Kamel, G.M. (2010) Pharmacokinetics and Tissue Distribution of Doxycycline in Broiler Chickens Pretreated with Either: Diclazuril or Halofuginone. Food and Chemical Toxicology, 48, 3209-3214. http://dx.doi.org/10.1016/j.fct.2010.08.024
[22]	Takahashi, I. and Yoshida, T. (1989) Antimycoplasmal Activities of Ofloxacin and Commonly Used Antimicrobial Agents on Mycoplasma gallisepticum. Japanese Journal of Antibiotics, 42, 1166-1172.
[23]	Bryant, J.E., Brown, M.P., Gronwall, R.R. and Merritt, K.A. (2000) Study of Intra-Gastric Administration of Doxycycline: Pharmacokinetics Including Body Fluid, Endometrial and Minimum Inhibitory Concentrations. Equine Veterinary Journal, 32, 233-238. http://dx.doi.org/10.2746/042516400776563608
[24]	Aronson, A.L. (1980) Pharmacotherapeutics of the Newer Tetracycline. Journal of the American Veterinary Medical Association, 176, 1061-1068.
[25]	Moskowitz, S.M., Foster, J.M., Emerson, J. and Burns, J.L. (2004) Clinically Feasible Biofilm Susceptibility Assay for Isolates of Pseudomonas aeruginosa from Patients with Cystic Fibrosis. Journal of Clinical Microbiology, 42, 1915-1922. http://dx.doi.org/10.1128/JCM.42.5.1915-1922.2004
[26]	Hoelscher, A.A., Bahcall, J.K. and Maki, J.S. (2006) In Vitro Evaluation of the Antimicrobial Effects of a Root Canal Sealer-Antibiotic Combination against Enterococcus faecalis. Journal of Endodontics, 32, 145-147. http://dx.doi.org/10.1016/j.joen.2005.10.031
[27]	Santos, M.D., Vermeersch, H., Remon, J.P., Schelkens, M., De Backer, P., Bree, H.J.J., et al. (1996) Pharmacokinetics and Bioavai-lability of Doxycycline in Turkeys. Journal of Veterinary Pharmacology and Therapeutics, 19, 274-280. http://dx.doi.org/10.1111/j.1365-2885.1996.tb00049.x
[28]	Baert, K., Croubels, S., Gasthuys, F., De Busser, J. and De Backer, P. (2000) Pharmacokinetics and Oral Bioavailability of Doxycycline Formulation (Doxycyc-line 75%) in Non-Fasted Young Pigs. Journal of Veterinary Pharmacology and Therapeutics, 23, 45-48. http://dx.doi.org/10.1046/j.1365-2885.2000.00235.x
[29]	Alvinerie, M., Lacoste, E., Sutra, J.F. and Chartier C. (1999) Some Pharmacokinetic Parameters of Eprinomectin in Goats Following Pour-On Administration. Veterinary Research Communications, 23, 449-455. http://dx.doi.org/10.1023/A:1006373609314
[30]	Ozdemir, N. and Yildirim, M. (2006) Bioequivalence Study of Two Long-Acting Oxytetracycline Formulations in Sheep. Veterinary Research Communications, 30, 929-934. http://dx.doi.org/10.1007/s11259-006-3235-2