1887

Abstract

The aim of this study was to investigate the urinary pharmacokinetics (PK) of orbifloxacin (OBFX) administered at 5 mg kg in six healthy dogs. A further aim was to use an model to evaluate the urinary PK and pharmacodynamics (PD) of OBFX to determine its urinary bactericidal titre (UBT), which represents the maximal dilution of urine allowing bactericidal activity.

Fourteen urinary tract infection (UTI) pathogenic strains of five bacterial species (, , , and ) were used. Urine samples were obtained every 4 h for the first 24 h after OBFX administration, for measurement of urine drug concentration and UBT.

The urine OBFX concentration peaked at 0–4, 4–8 or 4–8 h after administration, with a maximum concentration of 383±171 µg ml. Overall, the fluctuation in median UBT closely correlated with that of the mean urine OBFX concentration. In addition, the median areas under the UBT-time curves (AUBTs) were significantly inversely correlated with the MICs for OBFX in the tested strains (<0.01). Notably, median UBTs and AUBTs were extremely low (0–0.5 and 2–5, respectively) in OBFX-resistant strains with MIC ≥8 µg ml.

The fluctuation of UBTs closely correlated with that of urine concentration, and UBT values depended on the susceptibility of the bacterial strains to OBFX. We believe that modelling to determine UBTs is useful to evaluate the urinary PK/PD of antimicrobials indicated for UTIs in dogs.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.000476
2017-05-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jmm/66/5/616.html?itemId=/content/journal/jmm/10.1099/jmm.0.000476&mimeType=html&fmt=ahah

References

  1. Thompson MF, Litster AL, Platell JL, Trott DJ. Canine bacterial urinary tract infections: new developments in old pathogens. Vet J 2011; 190:22–27 [View Article][PubMed]
    [Google Scholar]
  2. Ling GV, Norris CR, Franti CE, Eisele PH, Johnson DL et al. Interrelations of organism prevalence, specimen collection method, and host age, sex, and breed among 8,354 canine urinary tract infections (1969–1995). J Vet Intern Med 2001; 15:341–347[PubMed]
    [Google Scholar]
  3. Smee N, Loyd K, Grauer G. UTIs in small animal patients: part 1: etiology and pathogenesis. J Am Anim Hosp Assoc 2013; 49:1–7 [View Article][PubMed]
    [Google Scholar]
  4. Weese JS, Blondeau JM, Boothe D, Breitschwerdt EB, Guardabassi L et al. Antimicrobial use guidelines for treatment of urinary tract disease in dogs and cats: antimicrobial guidelines working group of the international society for companion animal infectious diseases. Vet Med Int 2011; 2011:1–9 [View Article][PubMed]
    [Google Scholar]
  5. Wagenlehner FM, Naber KG. Antibiotic treatment for urinary tract infections: pharmacokinetic/pharmacodynamic principles. Expert Rev Anti Infect Ther 2004; 2:923–931 [View Article][PubMed]
    [Google Scholar]
  6. Wagenlehner FM, Wagenlehner C, Redman R, Weidner W, Naber KG. Urinary bactericidal activity of doripenem versus that of levofloxacin in patients with complicated urinary tract infections or pyelonephritis. Antimicrob Agents Chemother 2009; 53:1567–1573 [View Article][PubMed]
    [Google Scholar]
  7. Cazedey ECL, Salgado HRN. Orbifloxacin: a review of properties, its antibacterial activities, pharmacokinetic/pharmacodynamic characteristics, therapeutic use, and analytical methods. Crit Rev Anal Chem 2013; 43:79–99 [View Article]
    [Google Scholar]
  8. Food Drug Administration 2001; Guidance for industry, Bioanalytical Method Validation. www.fda.gov/downloads/Drugs/Guidance/ucm070107.pdf#search=%27Bioanalytical+Method+Validation%2C+Center+for+Drug+Evaluation+and+Research.%27 [Accessed on Jan 15, 2016]
  9. Harada K, Arima S, Niina A, Kataoka Y, Takahashi T. Characterization of Pseudomonas aeruginosa isolates from dogs and cats in japan: current status of antimicrobial resistance and prevailing resistance mechanisms. Microbiol Immunol 2012; 56:123–127 [View Article][PubMed]
    [Google Scholar]
  10. Harada K, Niina A, Nakai Y, Kataoka Y, Takahashi T. Prevalence of antimicrobial resistance in relation to virulence genes and phylogenetic origins among urogenital Escherichia coli isolates from dogs and cats in japan. Am J Vet Res 2012; 73:409–417 [View Article][PubMed]
    [Google Scholar]
  11. Harada K, Niina A, Shimizu T, Mukai Y, Kuwajima K et al. Phenotypic and molecular characterization of antimicrobial resistance in Proteus mirabilis isolates from dogs. J Med Microbiol 2014; 63:1561–1567 [View Article][PubMed]
    [Google Scholar]
  12. Clinical and Laboratory Standards Institute Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals; Approved Standard-Fourth Edition, CLSI document VET01-A4. Wayne, PA: 2013
    [Google Scholar]
  13. Clinical and Laboratory Standards Institute Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals; Second Informational Supplement, CLSI document VET01-S2. Wayne, PA: 2013
    [Google Scholar]
  14. Clinical and Laboratory Standards Institute Method for Determining Bactericidal Activity of Antimicrobial Agents; Approved Guideline, CLSI Document M26-A. Wayne, PA: 1999
    [Google Scholar]
  15. Well M, Naber KG, Kinzig-Schippers M, Sörgel F. Urinary bactericidal activity and pharmacokinetics of enoxacin versus norfloxacin and ciprofloxacin in healthy volunteers after a single oral dose. Int J Antimicrob Agents 1998; 10:31–38 [View Article][PubMed]
    [Google Scholar]
  16. Matsumoto S, Takahashi M, Yoshida M, Komatsu T, Kitadai Y et al. Absorption, distribution and excretion of orbifloxacin in dogs and cats. Jpn J Vet Med Assoc 1997; 50:470–474 [View Article]
    [Google Scholar]
  17. Heinen E. Comparative serum pharmacokinetics of the fluoroquinolones enrofloxacin, difloxacin, marbofloxacin, and orbifloxacin in dogs after single oral administration. J Vet Pharmacol Ther 2002; 25:1–5 [View Article][PubMed]
    [Google Scholar]
  18. Monlouis JD, de Jong A, Limet A, Richez P. Plasma pharmacokinetics and urine concentrations of enrofloxacin after oral administration of enrofloxacin in dogs. J Vet Pharmacol Ther 1997; 20:61–63 [CrossRef]
    [Google Scholar]
  19. Brown SA. Fluoroquinolones in animal health. J Vet Pharmacol Ther 1996; 19:1–14 [View Article][PubMed]
    [Google Scholar]
  20. Wagenlehner FM, Kinzig-Schippers M, Tischmeyer U, Wagenlehner C, Sörgel F et al. Urinary bactericidal activity of extended-release ciprofloxacin (1,000 milligrams) versus levofloxacin (500 milligrams) in healthy volunteers receiving a single oral dose. Antimicrob Agents Chemother 2006; 50:3947–3949 [View Article][PubMed]
    [Google Scholar]
  21. Turnidge J, Paterson DL. Setting and revising antibacterial susceptibility breakpoints. Clin Microbiol Rev 2007; 20:391–408 [View Article][PubMed]
    [Google Scholar]
  22. Miyazaki S, Matsui T, Arakawa S, Kamidono S, Maeda Y et al. Antibacterial activity of pazufloxacin in urine after administration to healthy volunteers. Jap J Chemother 1996; 44:90–95
    [Google Scholar]
  23. Drobot GR, Karlowsky JA, Hoban DJ, Zhanel GG. Antibiotic activity in microbiological media versus that in human urine: comparison of ampicillin, ciprofloxacin, and trimethoprim-sulfamethoxazole. Antimicrob Agents Chemother 1996; 40:237–240[PubMed]
    [Google Scholar]
  24. Hofbauer H, Naber KG, Kinzig-Schippers M, Sörgel F, Rustige-Wiedemann C et al. Urine bactericidal activity of pefloxacin versus norfloxacin in healthy female volunteers after a single 800-mg oral dose. Infection 1997; 25:121–126 [View Article][PubMed]
    [Google Scholar]
  25. Naber KG. Which fluoroquinolones are suitable for the treatment of urinary tract infections?. Int J Antimicrob Agents 2001; 17:331–341 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.000476
Loading
/content/journal/jmm/10.1099/jmm.0.000476
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error