A Novel In Vitro Pharmacokinetic/Pharmacodynamic Model Based on Two-Compartment Open Model Used to Simulate Serum Drug Concentration-Time Profiles

Access this Article

Author(s)

Abstract

An in vitro pharmacokinetic/pharmacodynamic perfusion model that simulates a two-compartment open model of serum drug concentration-time profiles following intravenous bolus injection and infusion was developed and mathematically described. In the present apparatus model, flow was kept in a one-way mode to avoid liquid traffic, and the washout effect seen in dilution models was overcome by embedding the tested bacteria in low melting point agarose gel. The validity of the equations and the reproducibility of the apparatus model were ascertained by simulating the concentration-time profiles of cefazolin and fosfomycin by substitution of their pharmacokinetic parameters obtained from humans for the equations. An empirical regimen 1X(q24h) of 1 g with cefazolin administered by intravenous infusion effectively killed a Staphylococcus aureus strain. The same regimen with fosfomycin produced a marked kill-curve with a fosfomycin-susceptible enterohaemorrhagic Escherichia coli O157:H7, whereas considerable regrowth was observed with a resistant strain. These results indicated that the present model was able to provide a convenient and reliable method for evaluating the efficacy of antimicrobial agents administered by intravenous infusion.

Journal

  • Microbiology and Immunology

    Microbiology and Immunology 51(5), 567-575, 2007-05-20

    Center for Academic Publications Japan

References:  26

Codes

  • NII Article ID (NAID)
    10020280446
  • NII NACSIS-CAT ID (NCID)
    AA00738350
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    03855600
  • NDL Article ID
    8721700
  • NDL Source Classification
    ZS9(科学技術--医学--病理学・微生物学・寄生虫学・感染・免疫学・血清学・アレルギー)
  • NDL Call No.
    Z53-M387
  • Data Source
    CJP  NDL  IR 
Page Top