Prediction of clinical bacteriological efficacy of oral antibiotics using a mechanism-based pharmacokinetic-pharmacodynamics modeling

DOI Web Site

書誌事項

公開日
2014-02-25
DOI
  • 10.11553/antibiotics.67.1_33
公開者
公益財団法人 日本感染症医薬品協会

この論文をさがす

説明

<p>The objective of this study was to predict the clinical bacteriological efficacy of antibiotics and to examine the pharmacodynamics (PD) characteristics of antibiotics against bacterial strains using a mechanism-based pharmacokinetic pharmacodynamics (PK-PD) modeling developed on the basis of interaction between drug concentrations and antibacterial activities.</p><p>Dynamic PD parameters (ε, γ, EC50) and growth rate of organisms (λ) were obtained from in vitro time-kill profile data of oral antibiotics, tebipenem pivoxil (TBPM-PI) and cefditoren pivoxil (CDTR-PI) against Streptococcus pneumoniae or Haemophilus influenze. PD characteristics of both drugs against S. pneumoniae or H. influenzae were examined, which indicated TBPM was concentration dependent as well as time-dependent, and CDTR was mainly time-dependent to exhibit their bactericidal activities. Next, we simulated TBPM and CDTR concentrations in plasma after oral administration according to the dosage regimen of each drug specified in package insert, using population pharmacokinetic parameters of both drugs in pediatric patients with infections. In addition, changes in viable in vivo bacterial counts in humans were simulated using dynamic PD parameters and mean plasma concentrations of each drug. As a result, simulated profile of viable counts of S. pneumoniae and H. influenzae were well corresponding to the bacteriological efficacy results in clinical double-blinded comparative study of TBPM-PI and CDTR-PI in oral administration to pediatric patients with acute otitis media.</p><p>As mentioned in the above, it was considered to be possible to clarify the PD characteristics of TBPM and CDTR against each bacterial strain using the mechanism-based PK-PD model developed on the basis of interaction between drug concentrations and antibacterial activities, and to estimate the clinical bacteriological efficacy of those drugs.</p>

収録刊行物

詳細情報 詳細情報について

問題の指摘

ページトップへ