IN-VIVO AND IN-VITRO STUDY OF SEVERAL PHARMACODYNAMIC EFFECTS OF MEROPENEM

Several pharmacodynamic parameters are being studied and applied to th e design of dosage regimens. The thigh infection model in neutropenic mice has been used in this study to investigate the in vivo postantibi otic effect (PAE) of meropenem against S. aureus, E. coli and P. aerug inosa. The sub-minimum inhibitory concentration (sub-MIC) postantibiot ic effect (PA SME) of 1/2, 1/4 and 1/8 x MIC was also determined in vi tro on S. aureus and E. coli after pre-exposure of these microorganism s to 10 x MIC of meropenem. The in vitro PAE was also determined. In v ivo killing curves using 2 different short dosage regimens were also s tudied to relate the lethal effect to the time that serum levels were above the MIC. No significant in vivo and in vitro PAEs were observed. The PA SMEs were higher for S. aureus than for E. coli. The 2 short d osage regimens, in vivo, were equally effective in killing S. aureus, but not E. coli. These results suggest that the pharmacodynamics of me ropenem on Gram-negative strains may need further study to elucidate t he mechanisms and characteristics of these parameters. On the other ha nd, we need to standardize a reliable in vitro method to monitor regro wth with a good correlation with the in vivo conditions.