Rational dosing of antibiotics: the use of plasma concentrations versus tissue concentrations.
At the moment, the most common pharmacokinetic/pharmacodynamic (PK/PD) approaches for anti-infective agents, such as time above MIC, C(max)/MIC and AUC(24)/MIC, rely on plasma concentration as the PK input value and minimum inhibitory concentration (MIC) as the PD input value. However, only the free tissue concentrations of antibiotics at the target site are responsible for the therapeutic effect. Using plasma concentrations frequently overestimates the target site concentrations and therefore clinical efficacy. Microdialysis is a new technique that allows direct measurement of unbound tissue concentrations. Furthermore, a better PD approach, bacterial time-kill curves, can offer more detailed information about the antibacterial activity as a function of time and antibiotic concentration than MICs.
Liu
Ping
P
Department of Pharmaceutics, College of Pharmacy, University of Florida, 1600 SW Archer Road, P.O. Box 100494, Gainesville 32610, USA.
Müller
Markus
M
Derendorf
Hartmut
H
D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D001419:Bacteria / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008826:Microbial Sensitivity Tests; D017551:Microdialysis / Q000379:methods; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents