The pharmacokinetic-pharmacodynamic approach to a rational dosage regimen for antibiotics

Res Vet Sci. 2002 Oct;73(2):105-14. doi: 10.1016/s0034-5288(02)00039-5.

Abstract

Pharmacokinetic-pharmacodynamic (PK/PD) surrogate indices (AUIC, AUC/MIC, C(max)/MIC, T>MIC) for measuring antibiotic efficacy are presented and reviewed. As clinical trials are not sufficiently sensitive to establish a dosage regimen which guarantees total bacteriological cure (Pollyanna phenomenon), PK/PD indexes have been proposed from in vitro, ex vivo, and in vivo infection models and subsequently validated in retrospective or prospective human clinical trials. The target value for time-dependent antibiotics (beta-lactams, macrolides) is a time above the MIC (T>MIC) of 50-80% of the dosage interval, while for concentration-dependent antibiotics (quinolones and aminoglycosides), the area under the inhibitory curve (AUIC, or more simply AUC/MIC of about 125h) is the best surrogate indicator of activity. Using the latter drugs, high concentrations achieved early during therapy are desirable to prevent the development of resistance. A C(max)/MIC ratio greater than 10-12 seems to be an appropriate target for aminoglycosides.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Infections / drug therapy*
  • Bacterial Infections / microbiology
  • Bacterial Infections / veterinary
  • Clinical Trials as Topic / veterinary
  • Drug Administration Schedule / veterinary
  • Drug Resistance, Bacterial
  • Humans
  • Microbial Sensitivity Tests / veterinary
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents