1: Int J Antimicrob Agents  2001;18 Suppl 1:S17-23

Macrolides: pharmacokinetics and pharmacodynamics.

Van Bambeke F, Tulkens PM.

Unite de Pharmacologie Cellulaire et Moleculaire, Universite catholique de
Louvain, UCL 73.70, Avenue E. Mounier 73, B-1200 Brussels, Belgium.

Three pharmacokinetic/pharmacodynamic parameters--(i) the peak concentration to
the minimum inhibitory concentration ratio (C(max)/MIC); (ii) the area under the
concentration-time curve to MIC ratio (AUC(24h)/MIC); and (iii) the time the
concentration exceeds the MIC (T>MIC)--are important predictors of the clinical
efficacy of antibiotics. For antibiotics with pronounced concentration-dependent
killing, such as the fluoroquinolones or the aminoglycosides, C(max)/MIC and
AUC(24)/MIC are the main factors that establish efficacy. Antibiotics with a
weak, or no, concentration dependency generally have their efficacy linked to
T>MIC, and these include the beta-lactams and the conventional macrolides.
Antibiotics with weak concentration-dependent effects, but with prolonged
persistent effects, such as tetracyclines and azithromycin, have their activity
mostly related to the AUC(24)/MIC. By applying these concepts to current
antibiotics, and also to the development of novel agents, it is possible to
optimise their dosages and administration schedules. This will maximise
therapeutic efficacy, may prevent or delay the emergence of bacterial resistance
to antibiotics, and can certainly minimise side-effects.

PMID: 11574190 [PubMed - in process]