Development and pharmacokinetic evaluation of chewable doxycycline tablets in Beagle dogs: comparison with a commercial formulation and evaluation of co-administration with vitamin supplement on the bioavailability


doxicilina, comprimidos mastigáveis, palatabilidade, farmacocinética. doxycycline, chewable tablets, palatability, pharmacokinetic.

How to Cite

Lima, I. de P., Magalhães, V. de S., de Oliveira, R. M., Ferreira, T. P., dos Santos, G. C. M., Alves, M. C. C., Pereira, G. A., da Silva, F. C. S., Rodrigues, L. F., Borges, D. A., de Oliveira, P. C., Scott, F. B., & Cid, Y. `Peluso. (2021). Development and pharmacokinetic evaluation of chewable doxycycline tablets in Beagle dogs: comparison with a commercial formulation and evaluation of co-administration with vitamin supplement on the bioavailability. Brazilian Journal of Veterinary Medicine, 43(1), e002921.


Doxycycline (DOX) is the antibiotic of choice for the treatment of canine monocytic ehrlichiosis (CME), one of the main infectious diseases affecting dogs. Despite the therapeutic simplicity, the need for long-term use of DOX tablets (28 days) and gastrointestinal effects may pose problems. The aim of the study was to develop a DOX chewable tablet, evaluate its palatability and pharmacokinetic profile in comparison with a commercial formulation, Doxifin®, and evaluate the influence of co-administration with vitamin supplement on the bioavailability of doxycycline. The AUC0-t values found for DOX chewable tablets (13.85 ± 3.81 μg.h/mL) and Doxifin® (15.88 ± 4.38 μg.h/mL) did not differ significantly (p<0.05). The co-administration of the vitamin supplement Hemolitan® influenced the pharmacokinetic profile of DOX, leading to a decrease in bioavailability for chewable DOX tablets and Doxifin®, with relative bioavailability values (F) of 64% and 62%, respectively. Palatability evaluations confirmed the palatability of the chewable tablets. Therefore, a DOX chewable tablet is an important alternative that can overcome some of the challenges associated with the characteristic bitter taste of doxycycline, with considerable reduction animal stress, and with plasma doxycycline concentrations equivalent in practical terms to a conventional product.


Brasil, Agência Nacional de Vigilância Sanitária – ANVISA. (2006). Guia para provas de biodisponibilidade relativa/bioequivalência de medicamentos (Resolução - RDC nº 1,170, de 19 de abril de 2006). Diário Oficial da República Federativa do Brasil, seção 1(101). 29RE_1170_2006_COMP.pdf/52326927-c379-45b4-9a7e-9c5ecabaa16b.

Brasil, Agência Nacional de Vigilância Sanitária – ANVISA. (2012). Dispõe sobre os requisitos mínimos para validação de métodos bioanalíticos empregados em estudos com fins de registro e pós-registro de medicamentos (Resolução - RDC nº 27, de 17 de maio de 2012). Diário Oficial da República Federativa do Brasil, seção 1(73). http://portal.

Brasil. (2019). Brazilian pharmacopeia (6th ed., Vol. 1). São Paulo: Atheneu.

Cerkvenik Flajs, V., & Grabnar, I. (2002). Ivermectin pharmacokinetics. Slovenian Veterinary Research, 39, 167-178.

Fourie, J. J., Horak, I., Crafford, D., Erasmus, H. L., & Botha, O. J. (2015). The efficacy treatment of a generic doxycycline tablet in the of canine monocytic ehrlichiosis. Journal of the South African Veterinary Association, 86(1), 1-10. PMid:26018824.

Goodman, G. (2003). As bases farmacológicas da terapêutica (13. ed.). São Paulo: McGraw-Hill.

Gutiérrez, L., Velasco, Z., Vázquez, C., Vargas, D., & Sumano, H. (2012). Pharmacokinetics of an injectable long-acting formulation of doxycycline hyclate in dogs. Acta Veterinaria Scandinavica, 54(1), 35. http://dx.doi. org/10.1186/1751-0147-54-35. PMid:22682068.

Hojman, P., Eriksen, J., & Gehl, J. (2007). Tet-On inductin with doxycycline after gene transfer in mice: Sweetening of drinking water is not a good idea. Animal Biotechnology, 18(3), 183-188. PMid:17612841.

Hopkins, A. M., Wojciechowski, J., Abuhelwa, A. Y., Mudge, S., Upton, R. N., & Foster, D. J. R. (2017). Population pharmacokinetic model of doxycycline plasma concentrations using pooled study data. Antimicrobial Agents and Chemotherapy, 61(3), e02401-e02416. PMid:28052851.

Kaneko, J., Harvey, J., & Bruss, M. (2008). Clinical biochemistry of domestic animals (6th ed.). Academic Press.

KuKanich,, K., & KuKanich, B. (2015). The effect of sucralfate tablets vs. suspension on oral doxycycline absorption in dogs. Journal of Veterinary Pharmacology and Therapeutics, 38(2), 169-173. PMid:25233871.

Monsalve, S., Galego, V., Molina, V. M., & Rodas, J. (2017). Pharmacokintics and adverse effects of doxycycline in the treatment of Ehrlichiosis: theoretical foundations for clinical trials in canines. Revista Mvz Cordoba, 22, 6062-6074.

Neer, T. M., Breitschwerdt, E. B., Greene, R. T., & Lappin, M. R. (2002). Consensus statement on ehrlichial disease of small animals from the infectious disease study group of the ACVIM. Journal of Veterinary Internal Medicine, 16(3), 309-315. PMid:12041661.

Okerman, L., Croubels, S., Cherlet, M., De Wasch, K., De Backer, P., & Van Hoof, J. (2004). Evaluation and establishing the performance of different screening tests for tetracycline residues in animal tissues. Food Additives and Contaminants, 21(2), 145-153. PMid:14754636.

Payne-Johnson, M., Maitland, T. P., Tilt, N., & Gossellin, J. (2007). An evaluation of the relative palatability of two comercial oral tablets formulations of carprofen and meloxicam in dogs using acceptance and preference tests. Revista Medicina Veterinaria, 158(10), 519-524.

Redelsperger, I. M., Taldone, T., Riedel, E. R., Lepherd, M. L., Lipman, N. S., & Wolf, F. R. (2016). Stability of doxycycline in feed and water and minimal effective doses in tetracycline-inducible systems. Journal of the American Association for Laboratory Animal Science, 55(4), 467-474. PMid:27423155.

Rinaldi, M. L. (2014). Therapeutic review: doxycycline. Journal of Exotic Pet Medicine, 23(1), 107-112.

Rudoler, N., Harrus, S., Martinez-Subiela, S., Tvarijonaviciute, A., van Straten, M., Cerón, J. J., & Baneth, G. (2015). Comparison of the acute phase protein and antioxidant responses in dogs vaccinated against canine monocytic ehrlichiosis and naïve-challenged dogs. Parasites & Vectors, 8(1), 175. PMid:25888870.

Ruiz, S. M. A., Olvera, L. G., Bernad, M. J. B., & Estrada, D. V. (2014). Pharmacokinetics of a new oral controlled-release formulation of doxycycline hyclate for dogs. Asian Journal of Pharmacology & Toxicology, 2(5), 1-6.

Sadrieh, N., Brower, J., Yu, L., Doub, W., Straughn, A., Machado, S., Pelsor, F., Martin, E. S., Moore, T., Reepmeyer, J., Toler, D., Nguyenpho, A., Roberts, R., Schuirmann, D. J., Nasr, M., & Buhse, L. (2005). Stability, dose uniformity, and palatability of three counterrrorism drugs-human subject and electronic tongue studies. Pharmaceutical Research, 22(10), 1747-1756. PMid:16180133.

Sainz, Á., Roura, X., Miró, G., Estrada-Peña, A., Kohn, B., Harrus, S., & Solano-Gallego, L. (2015). Guideline for veterinary practitioners on canine ehrlichiosis and anaplasmosis in Europe. Parasites & Vectors, 8(1), 75. PMid:25649069.

Shargel, L., & Yu, A. B. C. (2004). Applied biopharmaceutics & pharmacokinectics. São Paulo: McGraw-Hill.

Skotarczak, B. (2003). Canine ehrlichiosis. Annals of Agricultural and Environmental Medicine, 10(2), 137-141. PMid:14677903.

Song, Y., Peressin, K., Wong, P. Y., Page, S. W., & Garg, S. (2016). Key considerations in designing oral drug delivery systems for dogs. Journal of Pharmaceutical Sciences, 105(5), 1576-1585. PMid:27056627.

Thombre, A. G. (2004). Oral delivery of medications to companion animals: Palatability considerations. Advanced Drug Delivery Reviews, 56(10), 1399-1413. PMid:15191789.

Villaescusa, A., García-Sancho, M., Rodríguez-Franco, F., Tesouro, M. Á., & Sainz, Á. (2015). Effects of doxycycline on haematology, blood chemistry and peripheral blood lymphocyte subssets of healthy dogs and dogs naturally infected with Ehrlichia canis. Veterinary Journal (London, England), 204(3), 263-268. http://dx.doi. org/10.1016/j.tvjl.2015.03.031. PMid:25957920.

Weiss, D. J., & Wardrop, K. J. (2010). Schalm’s veterinary hematology (6th ed.). Ames: Wiley Blackwell.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright (c) 2021 Isabela de Paula Lima, Viviane de Souza Magalhães, Rodrigo Machado de Oliveira, Thais Paes Ferreira, Gabriela Carmelinda Martins dos Santos, Melina Cardilo Campos Alves, Geraldo Augusto Pereira, Fernanda Cristina Santos da Silva, Liliane Ferreira Rodrigues, Debora Azevedo Borges, Priscila Cardim de Oliveira, Fabio Barbour Scott, Yara `Peluso Cid