Pharmacokinetic parameters and optimal dosage of a florfenicol and tylosin mixture in beagle dogs A.F., Lee S.J., Park N.H., Park S.C. (2018): Pharmacokinetic parameters and optimal dosage of a florfenicol and tylosin mixture in beagle dogs. Veterinarni Medicina, 63: 329-334.
download PDF

The aims of this study were to evaluate the in vitro antibacterial activity of a florfenicol and tylosin mixture and to determine the pharmacokinetic parameters of each drug following administration of the 2 : 1 florfenicol and tylosin mixture in beagle dogs. The antibacterial activity of the two antibiotics, both singly and as a mixture, was investigated in bacteria isolated from 119 beagle dogs. Minimum inhibitory concentrations were determined using the broth dilution method, whereas the checkerboard assay was used to evaluate the antibacterial effects of the combination of florfenicol and tylosin. The pharmacokinetic parameters of the two antibiotics were determined following administration of the mixture in beagle dogs. Serum concentrations of both drugs were analysed using high-performance liquid chromatography. Pharmacokinetics parameters such as area under the concentration-time curve, absolute bioavailability and systemic clearance were determined using non-compartmental analysis. The results showed that tylosin and florfenicol exerted varying degrees of antibacterial activity against the tested isolates. The combination of florfenicol and tylosin produced a synergistic and additive antibacterial effect. Analysis of the serum samples revealed a rapid and almost complete absorption of florfenicol and tylosin with mean bioavailabilities of 92.7% and 106.1%, respectively. The times needed to reach maximum concentration for florfenicol and tylosin were 1.5 and 3 h, respectively. Moreover, intramuscular injection of the mixture to beagle dogs resulted in serum concentrations that were higher than the corresponding minimum inhibitory concentrations in beagle dogs. This is the first study to report optimisation of florfenicol and tylosin doses following administration of a combination of the two drugs to beagle dogs.

Ali BH, Al-Qarawi AA, Hashaad M (2003): Comparative plasma pharmacokinetics and tolerance of florfenicol following intramuscular and intravenous administration to camels, sheep, and goats. Veterinary Research Communications 27, 475–483.
AWJI Elias Gebru, DAMTE Dereje, LEE Seung-Jin, LEE Joong-Su, KIM Young-Hoan, PARK Seung-Chun (2012): The In Vitro Activity of 15 Antimicrobial Agents against Bacterial Isolates from Dogs. Journal of Veterinary Medical Science, 74, 1091-1094
Bonnier M, Dore C, Amedeo J, Guerin-Faublee V (2006): In vitro activity of tylosin and tilmicosin against cocci isolated from bovine mastitis. Revue de Medecine Veterinaire 157, 486–489.
CLSI – Clinical and Laboratory Standards Institute (2002): National committee for clinical laboratory standardization: Performance standards for antimicrobial disk and dilution susceptibility tests for bacteria isolated from animals; approved standard. 2nd edn. NCCLs document M31-A2. Wayne.
CLSI – Clinical and Laboratory Standards Institute (2012): Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard. 9th edn. Wayne.
Duthu Gwen S. (1985): Interspecies Correlation of the Pharmacokinetics of Erythromycin, Oleandomycin, and Tylosin. Journal of Pharmaceutical Sciences, 74, 943-946
Eliopoulos GM, Moellering RC (1991): Antimicrobial combinations. In: Lorian V (ed.): Antibiotics in Laboratory Medicine. 3rd edn. Williams and Wilkins, Baltimore. 432–492.
Ganiere J.-P., Medaille C., Mangion C. (2005): Antimicrobial Drug Susceptibility of Staphylococcus intermedius Clinical Isolates from Canine Pyoderma. Journal of Veterinary Medicine Series B, 52, 25-31
Gutierrez Martin César B., Rodriguez Ferri Elías F. (1993): In vitro susceptibility of Pasteurella multocida subspecies multocida strains isolated from swine to 42 antimicrobial agents. Zentralblatt für Bakteriologie, 279, 387-393
Hoekstra K.A., Paulton R.J.L. (2002): Clinical prevalence and antimicrobial susceptibility of Staphylococcus aureus and Staph. intermedius in dogs. Journal of Applied Microbiology, 93, 406-413
Isenberg HD (ed.) (1995): Identification methods: aerobic bacteriology. In: Clinical Microbiology Procedures Handbook. ASM Press, Washington, DC. 1–58.
Ji LW, Dong LL, Ji H, Feng XW, Li D, Ding RL, Jiang SX (2013): Comparative pharmacokinetics and bioavailability of tylosin tartrate and tylosin phosphate after a single oral and i.v. administration in chickens. Journal of Veterinary Pharmacology and Therapeutics 37, 312–315.
JIANG H.-X., ZENG Z.-L., CHEN Z.-L., LIU J. J., FUNG K.-F. (2006): Pharmacokinetics of florfenicol in pigs following intravenous, intramuscular or oral administration and the effects of feed intake on oral dosing. Journal of Veterinary Pharmacology and Therapeutics, 29, 153-156
KIM Mi-Hee, GEBRU Elias, CHANG Zhi-Qiang, CHOI Jae-Young, HWANG Mi-Hyun, KANG Eun-Hee, LIM Jong-Hwan, YUN Hyo-In, PARK Seung-Chun (2008): Comparative Pharmacokinetics of Tylosin or Florfenicol after a Single Intramuscular Administration at Two Different Doses of Tylosin-Florfenicol Combination in Pigs. Journal of Veterinary Medical Science, 70, 99-102
KIM Eun-Young, GEBRU Elias, LEE Joong-Su, KIM Jong-Choon, PARK Seung-Chun (2011): Pharmacokinetics of a Florfenicol-Tylosin Combination after Intravenous and Intramuscular Administration to Beagle Dogs. Journal of Veterinary Medical Science, 73, 463-466
Koc F., Ozturk M., Kadioglu Y., Dogan E., Yanmaz L.E., Okumus Z. (2009): Pharmacokinetics of florfenicol after intravenous and intramuscular administration in New Zealand White rabbits. Research in Veterinary Science, 87, 102-105
Liu J., Fung K.-F., Chen Z., Zeng Z., Zhang J. (2003): Pharmacokinetics of Florfenicol in Healthy Pigs and in Pigs Experimentally Infected with Actinobacillus pleuropneumoniae. Antimicrobial Agents and Chemotherapy, 47, 820-823
Marks S (2003): Antimicrobial susceptibilities of canine Clostridium difficile and Clostridium perfringens isolates to commonly utilized antimicrobial drugs. Veterinary Microbiology, 94, 39-45
Meletiadis J., Pournaras S., Roilides E., Walsh T. J. (2010): Defining Fractional Inhibitory Concentration Index Cutoffs for Additive Interactions Based on Self-Drug Additive Combinations, Monte Carlo Simulation Analysis, and In Vitro-In Vivo Correlation Data for Antifungal Drug Combinations against Aspergillus fumigatus. Antimicrobial Agents and Chemotherapy, 54, 602-609
Odland BA, Erwin ME, Jones RN (2000): Quality control guidelines for disk diffusion and broth microdilution antimicrobial susceptibility tests with seven drugs for veterinary applications. Journal of Clinical Microbiology 38, 453–455.
Park Byung-Kwon, Lim Jong-Hwan, Kim Myoung-Seok, Hwang Youn-Hwan, Yun Hyo-In (2008): Pharmacokinetics of florfenicol and its metabolite, florfenicol amine, in dogs. Research in Veterinary Science, 84, 85-89
Pedersen K., Pedersen K., Jensen H., Finster K., Jensen V. F., Heuer O. E. (2007): Occurrence of antimicrobial resistance in bacteria from diagnostic samples from dogs. Journal of Antimicrobial Chemotherapy, 60, 775-781
Prats C, El Korchi G, Francesch R, Arboix M, Pérez B (2002): Disposition kinetics of tylosin administered intravenously and intramuscularly to pigs. Research in Veterinary Science, 73, 141-144
Priebe S., Schwarz S. (2003): In Vitro Activities of Florfenicol against Bovine and Porcine Respiratory Tract Pathogens. Antimicrobial Agents and Chemotherapy, 47, 2703-2705
Pyörälä Satu, Baptiste Keith Edward, Catry Boudewijn, van Duijkeren Engeline, Greko Christina, Moreno Miguel A., Pomba M. Constança Matias Ferreira, Rantala Merja, Ružauskas Modestas, Sanders Pascal, Threlfall E. John, Torren-Edo Jordi, Törneke Karolina (2014): Macrolides and lincosamides in cattle and pigs: Use and development of antimicrobial resistance. The Veterinary Journal, 200, 230-239
Sams RA (1994): Florfenicol: chemistry and metabolism of a novel broad spectrum antibiotic. In: Proceedings of the XVIII World Buiatrics Congress, Bologna, Italy. 13–17.
Scott BA, Mortensen JE, McKeever TM, Logas DB, McKeever PJ (2010): Efficacy of tylosin tartrate on canine Staphylococcus intermedius isolates in vitro. Veterinary Therapeutics 11, 1–7.
TAHA A.A., ELSHEIKH H.A., KHALAFALLA A.E., OSMAN I.AM., ABDULLAH A.SALAM (1999): Disposition Kinetics of Tylosin Administered Intravenously and Intramuscularly in Desert Sheep and Nubian Goats. The Veterinary Journal, 158, 210-215
Vaara M (1993): Outer membrane permeability barrier to azithromycin, clarithromycin, and roxithromycin in gram-negative enteric bacteria.. Antimicrobial Agents and Chemotherapy, 37, 354-356
Weisel MK, Powers JD, Powers TE, Baggot JD (1977): A pharmacokinetic analysis of tylosin in the normal dog. American Journal of Veterinary Research 38, 273–275.
download PDF

© 2020 Czech Academy of Agricultural Sciences