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

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.
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Submitted on : Tuesday, September 14, 2010 - 10:53:35 PM
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  • HAL Id : hal-00517583, version 1
  • PUBMED : 12204627



Pierre-Louis Toutain, Jérome R. E. del Castillo, Alain Bousquet-Mélou. The pharmacokinetic-pharmacodynamic approach to a rational dosage regimen for antibiotics.. Research in Veterinary Science, Elsevier, 2002, 73 (2), pp.105-14. ⟨hal-00517583⟩



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