A two compartment in-vitro model was designed to simulate human pharmacokinetics and to expose bacterial cultures to changing drug concentrations, thereby avoiding limitations of conventional antibiotic testing at constant drug levels. Serially placed bacterial compartments, representing extravascular infection sites, interface with a central compartment through artificial capillaries. Drug concentrations within the culture chambers closely mimic interstitial concentrations in vivo. Simultaneous first order elimination kinetics of two drugs with different half-lives were simulated to study antibacterial effects of drug combinations. This in-vitro model is an efficient tool for optimal dosage regimen design and the study of synergistic/antagonistic effects of antibiotic combinations.