What have we learned from pharmacokinetic and pharmacodynamic theories?

Pharmacokinetic characteristics and pharmacodynamic properties dictate anti microbial response and, along with natural immune responses, clinical outco mes. As new agents are developed with long half-lives, we will lose the abi lity to differentiate between concentration-dependent and time-dependent pr operties. The area under the inhibitory concentration curve (AUIC) defines drug regimens as a ratio of drug exposure to minimum inhibitory concentrati on (MIC) and allows them to be compared with each other. With AUIC and agen ts with long half-lives, these comparisons are possible regardless of chemi cal classification or concentration or time-dependent activity. Historical examples of reduced drug exposure from decreased doses (i.e., cefaclor, cla rithromycin, and ciprofloxacin), and thus low AUIC values, directly correla te with drug resistance. In the face of rising MICs (as is occurring worldw ide with Streptococcus pneumoniae), close attention to appropriate dosing a nd concentration above the MIC may delay and potentially even prevent antib iotic resistance. Creating selective pressure on reliable antibiotics by in appropriately reducing their doses will undoubtedly challenge these agents and may destroy entire drug classes with similar mechanisms of action or re sistance.