ABSTRACT
There is a gap between antibiotic effects in the clinical setting and routine susceptibility testing and/or traditional time-kill studies at fixed concentrations of antibiotics: both reflect the intrinsic antibiotic activity but ignore pharmacokinetics. Being aware of these limitations, a way to simultaneously consider both factors was first suggested in 1966 by O’Grady and Pennington (1). They developed an in vitro model that simulates urinary excretion of antibiotics and exposes a bacterial culture to clinically achievable urinary drug concentrations. Soon after, in 1968, Sanfilippo and Morvillo (2) described another model that allows pharmacodynamic evaluation of sulfonamides by in vitro simulation of their pharmacokinetics in human serum. These innovative studies provided the impetus to further progress in this kind of modeling over the subsequent 15 years. The achievements were so imposing, especially in the area of model design, that a special meeting on the methodology and evaluation of in vitro dynamic models was organized by the Paul Ehrlich Society for Chemotherapy and the British Society for Antimicrobial Chemotherapy (Bad Honnef, 1984). Over the next 10 years, in vitro dynamic models were used in pharmacodynamic studies with many novel antibiotics, in particular those that exhibit different pharmacokinetics but similar intrinsic activities. Most of these studies demonstrated the very good potential of in vitro dynamic models rather than providing clinically useful findings. However, this experience led to the subsequent displacement of purely phenomenological studies by better designed, more predictive studies that have been reported over the past 10 years.
