Pharmacokinetics of florfenicol following intravenous and intramuscular administration in dogs

https://doi.org/10.17221/8247-VETMEDCitation:Birdane Y., Birdane F. (2015): Pharmacokinetics of florfenicol following intravenous and intramuscular administration in dogs. Veterinarni Medicina, 60: 323-329.
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Florfenicol is a synthetic broad-spectrum antibiotic used to treat infectious diseases in veterinary medicine. Limited information is available on the pharmacokinetics and bioavailability of florfenicol in dogs. This study was conducted in six healthy dogs to determine the bioavailability and pharmacokinetics of florfenicol following a single intravenous (i.v.) and intramuscular (i.m.) dose of 30 mg/kg body weight (b.w.). Blood samples were taken over the course of 24 h post-treatment and the recovered plasma was extracted and analysed using high-performance liquid chromatography (HPLC). Pharmacokinetic analysis was performed using a two-compartment open model. After i.v. administration of florfenicol, elimination half-life (t½b), volume of distribution at steady state (Vdss), total body clearance (ClT) and area under curve (AUC0–24) were 3.09 ± 0.13 h, 1.19 ± 0.15 l/kg, 0.37 ± 0.04 l/h/kg, and 59.44 ± 5.27 µg/h/ml, respectively. The peak plasma concentration (Cmax), time to maximum concentration (tmax) and bioavailability (F) were 3.05 ± 0.43 µg/ml, 1.50 ± 0.35 h, and 44.70 ± 6.75%, respectively, following i.m. administration. In this study the time that plasma concentration exceed the concentration of 1 µg/ml was approximately 8 h. Therefore, florfenicol should be given twice daily at a dosage of 30 mg/kg b.w. to maintain therapeutic concentration. The pharmacokinetic profile of florfenicol in dogs reveals that it may be therapeutically useful against susceptible microorganisms involved in most common infections in dogs.
References:
Abd El-Aty A.M., Goudah A., Abo El-Sooud K., El-Zorba H.Y., Shimoda M., Zhou H.-H. (2004): Pharmacokinetics and Bioavailability of Florfenicol Following Intravenous, Intramuscular and Oral Administrations in Rabbits. Veterinary Research Communications, 28, 515-524  https://doi.org/10.1023/B:VERC.0000040241.06642.49
 
Adams PE, Varma KJ, Powers TE, Lamendola JF (1987): Tissue concentrations and pharmacokinetics of florfenicol in male veal calves given repeated doses. American Journal of Veterinary Research 48, 1725–1732.
 
Alcorn J., Dowling P., Woodbury M., Killeen R. (2004): Pharmacokinetics of florfenicol in North American elk (Cervus elaphus). Journal of Veterinary Pharmacology and Therapeutics, 27, 289-292  https://doi.org/10.1111/j.1365-2885.2004.00594.x
 
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. https://doi.org/10.1023/A:1025741724701
 
Andes D., Craig W.A. (2002): Animal model pharmacokinetics and pharmacodynamics: a critical review. International Journal of Antimicrobial Agents, 19, 261-268  https://doi.org/10.1016/S0924-8579(02)00022-5
 
Atef M., El-Gendi A. Y., Amer A. A. M., El-Aty Abd (2001): Disposition Kinetics of Florfenicol in Goats by Using Two Analytical Methods. Journal of Veterinary Medicine Series A, 48, 129-136  https://doi.org/10.1046/j.1439-0442.2001.00339.x
 
Ayling R. D., Baker S. E., Nicholas R. A. J., Peek M. L., Simon A. J. (2000): Comparison of in vitro activity of danofloxacin, florfenicol, oxytetracycline, spectinomycin and tilmicosin against recent field isolates of Mycoplasma bovis. Veterinary Record, 146, 745-747  https://doi.org/10.1136/vr.146.26.745
 
Booker CW, Jim GK, Guichon PT, Schunicht OC, Thorlakson BE, Lockwood PW (1997): Evaluation of florfenicol for the treatment of undifferentiated fever in feedlot calves in western Canada. Canadian Veterinary Journal 38, 555–560.
 
BRETZLAFF K. N., NEFF-DAVIS C. A., OTT R. S., KORITZ G. D., GUSTAFSSON B. K., DAVIS L. E. (1987): Florfenicol in non-lactating dairy cows: pharmacokinetics, binding to plasma proteins, and effects on phagocytosis by blood neutrophils. Journal of Veterinary Pharmacology and Therapeutics, 10, 233-240  https://doi.org/10.1111/j.1365-2885.1987.tb00534.x
 
Cannon M., Harford S., Davies J. (1990): A comparative study on the inhibitory actions of chloramphenicol, thiamphenicol and some fluorinated derivatives. Journal of Antimicrobial Chemotherapy, 26, 307-317  https://doi.org/10.1093/jac/26.3.307
 
Castells G, Intorre L, Franquelo C, Cristofol C, Perez B, Marti G, Arboix M (1998): Pharmacokinetics of thiamphenicol in dogs. American Journal of Veterinary Research 59, 1473–1475.
 
Decraene BA, Deprez P, D’Haese E, Nelis HJ, Vannden Bossche W, Deleenheer AP (1997): Pharmacokinetics of florfenicol in cerebrospinal fluid and plasma of calves. Antimicrobial Agents and Chemotherapy 41, 1991–1995.
 
HO Shu-Peng, HSU Tain-Yao, CHEN Ming-Hui, WANG Way-Shyan (): Antibacterial Effect of Chloramphenicol, Thiamphenicol and Florfenicol against Aquatic Animal Bacteria.. Journal of Veterinary Medical Science, 62, 479-485  https://doi.org/10.1292/jvms.62.479
 
Jianzhong S., Xiubo L., Haiyang J., Walter H. H. (2004): Bioavailability and pharmacokinetics of florfenicol in healthy sheep*. Journal of Veterinary Pharmacology and Therapeutics, 27, 163-168  https://doi.org/10.1111/j.1365-2885.2004.00574.x
 
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  https://doi.org/10.1292/jvms.10-0243
 
Lane V. M., Wetzlich S., Clifford A., Taylor I., Craigmill A. L. (2004): Intravenous and subcutaneous pharmacokinetics of florfenicol in sheep. Journal of Veterinary Pharmacology and Therapeutics, 27, 191-196  https://doi.org/10.1111/j.1365-2885.2004.00580.x
 
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  https://doi.org/10.1128/AAC.47.2.820-823.2003
 
LOBELL R. D., VARMA K. J., JOHNSON J C, Sams R. A., GERKEN D. F., ASHCRAFT S. M. (1994): Pharmacokinetics of florfenicol following intravenous and intramuscular doses to cattle. Journal of Veterinary Pharmacology and Therapeutics, 17, 253-258  https://doi.org/10.1111/j.1365-2885.1994.tb00241.x
 
MacGowan AP, Bowker KE (1997): Pharmacodynamics of antimicrobial agents and rationale for their dosing. Journal of Chemotherapy 9, 64–73.
 
Marshall SA, Jones RN, Wanger A, Washington JA, Doern GV, Leber AL, Haugen TH (1996): Proposed MIC quality control guidelines for National Committee for Clinical Laboratory Standards susceptibility tests using seven veterinary antimicrobial agents: ceftiofur, enrofloxacin, florfenicol, penicillin G-novobiocin, pirlimycin, premafloxacin and spectinomycin. Journal of Clinical Microbiology 34, 2027–2029.
 
MCKELLAR Q. A., VARMA K. J. (1996): Pharmacokinetics and tolerance of florfenicol in Equidae. Equine Veterinary Journal, 28, 209-213  https://doi.org/10.1111/j.2042-3306.1996.tb03774.x
 
PARK B.-K., LIM J.-H., KIM M.-S., YUN H.-I. (2006): Pharmacokinetics of florfenicol and its metabolite, florfenicol amine, in the Korean catfish (Silurus asotus). Journal of Veterinary Pharmacology and Therapeutics, 29, 37-40  https://doi.org/10.1111/j.1365-2885.2006.00709.x
 
PARK B.-K., LIM J.-H., KIM M.-S., HWANG Y.-H., YUN H.-I. (2007): Pharmacokinetics of florfenicol and its major metabolite, florfenicol amine, in rabbits. Journal of Veterinary Pharmacology and Therapeutics, 30, 32-36  https://doi.org/10.1111/j.1365-2885.2007.00809.x
 
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  https://doi.org/10.1016/j.rvsc.2007.04.001
 
Pasmans F., Baert K., Martel A., Bousquet-Melou A., Lanckriet R., De Boever S., Van Immerseel F., Eeckhaut V., de Backer P., Haesebrouck F. (): Induction of the Carrier State in Pigeons Infected with Salmonella enterica Subspecies enterica Serovar Typhimurium PT99 by Treatment with Florfenicol: a Matter of Pharmacokinetics. Antimicrobial Agents and Chemotherapy, 52, 954-961  https://doi.org/10.1128/AAC.00575-07
 
Sams RA (1994): Florfenicol: chemistry and metabolism of a novel broadspectrum antibiotic. In: Proceedings of the XVIII World Buiatrics Congress, Bologna, Italy, 13–17.
 
SANDERS P., GUILLOT P., MOUROT D. (1988): Pharmacokinetics of a long-acting chloramphenicol formulation administered by intramuscular and subcutaneous routes in cattle. Journal of Veterinary Pharmacology and Therapeutics, 11, 183-190  https://doi.org/10.1111/j.1365-2885.1988.tb00139.x
 
Shen Jianzhong, Wu Xianai, Hu Dingfei, Jiang Haiyang (2002): Pharmacokinetics of florfenicol in healthy and Escherichia coli-infected broiler chickens. Research in Veterinary Science, 73, 137-140  https://doi.org/10.1016/S0034-5288(02)00033-4
 
Shen J., Hu D., Wu X., Coats J. R. (2003): Bioavailability and pharmacokinetics of florfenicol in broiler chickens. Journal of Veterinary Pharmacology and Therapeutics, 26, 337-341  https://doi.org/10.1046/j.1365-2885.2003.00495.x
 
Shumaker Robert C. (1986): PKCALC: A Basic Interactive Computer Program for Statistical and Pharmacokinetic Analysis of Data. Drug Metabolism Reviews, 17, 331-348  https://doi.org/10.3109/03602538608998295
 
SOBACK S., PAAPE M.J., FILEP R., VARMA K.J. (1995): Florfenicol pharmacokinetics in lactating cows after intravenous, intramuscular and intramammary administration. Journal of Veterinary Pharmacology and Therapeutics, 18, 413-417  https://doi.org/10.1111/j.1365-2885.1995.tb00618.x
 
SWITAŁA M., HRYNYK R., SMUTKIEWICZ A., JAWORSKI K., PAWLOWSKI P., OKONIEWSKI P., GRABOWSKI T., DEBOWY J. (2007): Pharmacokinetics of florfenicol, thiamphenicol, and chloramphenicol in turkeys. Journal of Veterinary Pharmacology and Therapeutics, 30, 145-150  https://doi.org/10.1111/j.1365-2885.2007.00827.x
 
Syriopoulou V P, Harding A L, Goldmann D A, Smith A L (1981): In vitro antibacterial activity of fluorinated analogs of chloramphenicol and thiamphenicol.. Antimicrobial Agents and Chemotherapy, 19, 294-297  https://doi.org/10.1128/AAC.19.2.294
 
Tautain PL, Del Castillo JRE, Bousquet-Melou A (2002): The pharmacokinetic-pharmacodynamic approach to a rational dosage regimen for antibiotics. Resarch in Veterinary Science 73, 105–114. 
 
UEDA Yuji, OHTSUKI Shigenobu, NARUKAWA Noriaki (1995): Efficacy of Florfenicol on Experimental Actinobacillus Pleuropneumonia in Pigs.. The Journal of Veterinary Medical Science, 57, 261-265  https://doi.org/10.1292/jvms.57.261
 
VARMA K.J., ADAMS P. E., POWERS T. E., POWERS J. D., LAMENDOLA J. F. (1986): Pharmacokinetics of florfenicol in veal calves. Journal of Veterinary Pharmacology and Therapeutics, 9, 412-425  https://doi.org/10.1111/j.1365-2885.1986.tb00062.x
 
Varma KJ, Adams PE, Powers TE, Powers JD, Lamendola JF (1998): Pharmacology, safety and clinical efficacy of Nuflor® (florfenicol) following subcutaneous administration to cattle. Cattle Practice 6, 281–286.
 
Wagner JG (1975): Fundamentals of Clinical Pharmacokinetics. Drug Intelligence Pub Inc, Illinois, USA.
 
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