Development of Software Support Tool for Planning Administration of Biapenem, a Carbapenem Antibacterial Agent, based on Pharmacokinetic/Pharmacodynamic Approach and Monte Carlo Simulation

In consideration of the proposal to base the rational use of biapenem, a carbapenem antibacterial agent, on pharmacokinetic/pharmacodynamic (PK/PD) theory, we created software to support the planning of biapenem administration based on a PK/PD approach using the Monte Carlo simulation. The software was created using a macro-program written in visual basic language for applications on Microsoft Excel. To predict values for the PK/PD parameters ‘time above the minimum inhibitory concentration (T>MIC)’ and probability of target attainment for approved biapenem dosage regimen against various bacteria populations, the Monte Carlo simulation was performed for 10000 subjects using the Crystal Ball® embedded pharmacokinetic program MULTI-Win. Variability in pharmacokinetic parameters and MIC distributions were obtained using OMEGACIN® package insert data and data from a nationwide antibiotics-susceptibility test surveillance program, respectively. When the software was used for a patient with severe pneumonia and renal failure who was undergoing haemodialysis, several dosage regimens were recommended based on T>MIC predicted from the patient's data, thereby demonstrating its clinical usefulness. Our software proved effective as a tool for supporting biapenem administration planning for individual patients, and rational use based on PK/PD theory concerning antimicrobial agents.