The pharmacokinetic-pharmacodynamic approach to a rational dosage regimen for antibiotics. - Archive ouverte HAL
Article Dans Une Revue Research in Veterinary Science Année : 2002

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

Résumé

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.

Domaines

Pharmacologie

Dates et versions

hal-00517583 , version 1 (14-09-2010)

Identifiants

Citer

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, 2002, 73 (2), pp.105-14. ⟨10.1016/S0034-5288(02)00039-5⟩. ⟨hal-00517583⟩
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