Abstract
Carbapenems have potent antibacterial effects and are widely used for the treatment of various infections.The activity of carbapenems is time dependent, and the antibacterial and therapeutic effects correlate with the duration of exposure to a drug concentration above the minimum inhibitory concentration for the bacterium (T>MIC), particularly the concentration in the target organ. Based on these pharmacokinetic/pharmacodynamic (PK/PD) properties, carbapenem regimens should be optimized to maximize the efficacy. However, measurement of drug concentrations of carbapenems in biological samples had been difficult, and there was no easy-to-use PK/PD software that supports carbapenem therapy. Thus, we developed simple methods for measuring blood concentrations of meropenem, biapenem, doripenem and imipenem, and reported their population PK parameters in Japanese patients. We also developed a new software with Monte Carlo simulation technique to calculate the probabilities of therapeutic target attainment for different regimens against various pathogens. Moreover, we examined in detail the drug disposition of carbapenems in target tissues such as peritoneal fluid, cerebrospinal fluid, bile and prostatic tissue. These results contribute to the proper use of carbapenems based on the PK/PD theory. ( Jpn J Clin Pharmacol Ther 2012; 43(4): 209-214)
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