Disposition Kinetics of Difloxacin After Intravenous, Intramuscular and Subcutaneous Administration in Calves
Tóm tắt
The pharmacokinetics of difloxacin (Dicural) was studied in a crossover study using three groups (n = 4) of male and female Friesian calves after intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administrations of 5 mg/kg body weight. Drug concentration in plasma was determined by high-performance liquid chromatography using fluorescence detection. The plasma concentration–time data following i.v. administration were best fitted to a two-compartment open model and those following i.m. and s.c. routes were best fitted using one-compartment open model. The collected data were subjected to a computerized kinetic analysis. The mean i.v., i.m. and s.c. elimination half-lives (t
1/2β) were 5.56 ± 0.33 h, 6.12 ± 0.42 h and 7.26 ± 0.6 h, respectively. The steady-state volume of distribution (V
dss) was 1.12 ± 0.09 L/kg and total body clearance (ClB) was 2.19 ± 0.1 ml/(min. kg). The absorption half lives (t
1/2ab) were 0.38 ± 0.027 h and 2.1 ± 0.09 h, with systemic bioavailabilities (F) of 96.5% ± 6.4% and 84% ± 5.5% after i.m. and s.c. administration, respectively. After i.m. and s.c. dosing, peak plasma concentrations (C
max) of 3.38 ± 0.13 μg/ml and 2.18 ± 0.12 μg/ml were attained after (t
max) 1.22 ± 0.20 h and 3.7 ± 0.52 h. The MIC90 of difloxacin for Mannheimia haemolytica was 0.29 ± 0.04 μg/ml. The AUC/MIC90 and C
max/MIC90 ratios for difloxacin following i.m. administration were 120 and 11.65, respectively and following s.c. administration were 97.58 and 7.51, respectively. Difloxacin was 31.7–36.8% bound to calf plasma protein. Since fluoroquinolones display concentration-dependent activities, the doses of difloxacin used in this study are likely to involve better pharmacodynamic characteristics that are associated with greater clinical efficacy following i.m. administration than following s.c. administration.
Tài liệu tham khảo
Abd el Aty, A.M., Goudah, A., Ismail, M. and Shimoda, M., 2005. Disposition kinetics of difloxacin in rabbits after intravenous and intramuscular injection of Dicural. Veterinary Research Communications, 29, 297–304
Atef, M., El Banna, H.A., Abd El Aty, A.M. and Goudah, A., 2002. Pharmacokinetics of difloxacin in goats. Deutsche Tierarztliche Wochenschrift, 109, 320–323
Baggot, J.D., 1978. Some aspects of clinical pharmacokinetics in veterinary medicine. Journal of Veterinary Pharmacology and Therapeutics, 1, 5–18
Brown, S.A., 1996. Fluoroquinolones in animal health. Journal of Veterinary Pharmacology and Therapeutics, 19, 1–14
Chu, D.T., Granneman, G.R. and Fernandes, P.B., 1985. Abbott-56619. Drug Future, 10, 543–545
Dalhoff, A. and Ullmann, U., 1990. Correlation between pharmacokinetics, pharmacodynamics and efficacy of antibacterial agents in animal models. European Journal of Clinical Microbiology and Infectious Diseases, 9, 479–487
Davidson, J.N., Conzleman, G.M. and Baggot, J.D., 1986. Pharmacokinetics of enrofloxacin in preruminant and ruminant claves. Proceedings of the Western Pharmacological Society, 29, 129–132
Digranes, A. and Dibb, W., 1986. In vitro activities of A-56619 (Difloxacin) and A 65520, two aryl fluoroquinolones. Chemotherapy, 34, 298–307
Drlica, K. and Zhao, X., 1997. DNA gyrase, topoisomerase IV, and the 4-quinolines. Microbiology and Molecular Biology Review, 61, 377–392
Fernandes, P.B., 1988. Mode of action and in vitro and in vivo activities of the fluoroquinolones. Journal of Clinical Pharmacology, 28, 156–168
Forrest, A., Nix, D.E. and Ballow, A., 1993. Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrobial Agents and Chemotherapy, 37, 1073–1081
Frazier, D.L., Thompson, L., Terettien, A. and Evans, E.I., 2000. Comparison of fluoroquinolone pharmacokinetic parameters after treatment with marbofloxacin, enrofloxacin and difloxacin in dogs. Journal of Veterinary Pharmacology and Therapeutics, 23, 293–302
Gibaldi, M. and Perrier, D., 1982. Non compartmental analysis based on statistical moment theory. Pharmacokinetics, 2nd edn, (Marcel Dekker, New York), 409–424
Granneman, G.R., Synder, K.M and Shu, V.S., 1986. Difloxacin metabolism and pharmacokinetics in human after oral doses. Antimicrobial Agents and Chemotherapy, 30, 689–693
Heinen, E., 2002. Comparative serum pharmacokinetics of enrofloxacin and difloxacin as well as their main metabolites in dogs. Journal of Veterinary Pharmacology and Therapeutics, 25, 1–5
Inui, T., Taira, T., Matsushita, T. and Endo, T., 1998. Pharmacokinetic properties and oral bioavailabilities of difloxacin in pig and chicken. Xenobiotica, 28, 887–893
Jones, R.N, Barry, A.L., Govan, T.L. and Washington, J.A., 1985. Susceptibility tests, microdilution and macrodilution broth procedures. In: Lannette, E.H, Alaws, A.B, Hausler, W.J. and Shouldomy, H.J. (eds.), Manual of Clinical Microbiology (American Society for Microbiology, Washington, DC), 972–977
Mader, I.T., Morrison, L.T. and Admas, K.R., 1987. Comparative evaluation of A-56619 (Difloxacin) and Nafcillin in the treatment of experimental Staphylococcus aureus osteomyelitis. Antimicrobial Agents and Chemotherapy, 34, 310–316
Mann, D.D. and Frame, G.M., 1992. Pharmacokinetic study of danofloxacin in cattle and swine. American Journal of Veterinary Research, 53, 1022–1026
Singhvi, S.M., Heald, A.F., Gadebusch, H.H., Resnick, M.E., Ditazio, L.T. and Leitz, M.A., 1977. Human serum protein binding of cephalosporin antibiotics in vitro. Journal of Laboratory and Clinical Medicine, 89, 414–420
Sullivan, M.C., Cooper, B.W., Nightingale, C.H., Quintiliani, R. and Lawlor, M.T., 1993. Evaluation of the efficacy of ciprofloxacin against Streptococus pneumoniae by using a mouse protection model. Antimicrobial Agents and Chemotherapy, 37, 234–239
Vogelman, B., Gudmundsson, S. and Leggett, J., 1988. Correlation of antibacterial pharmacokinetic parameters with therapeutic efficacy in animal models. Journal of Infectious Diseases, 158, 831–847
Walker, R.D., 2000. Fluoroquinolones. In: Prescot, J.F., Baggot, J.D. and Walker, R.D. (eds), Antimicrobial Therapy in Veterinary Medicine, 3rd edn (Iowa State University Press, Ames, IA)
Wolfson, J.S. and Hooper D.C., 1989. Fluoroquinolone antimicrobial agents. Clinical Microbiology Reviews, 2, 378–424