Vol.54 No.5 September 2006
Relationship of oral cephem antibiotics to rat thigh muscle concentrations and therapeutic efficacy against rat thigh infection
Discovery Research Laboratories, Shionogi & Co., Ltd.,
3-1-1 Futaba-cho, Toyonaka, Osaka, Japan
Abstract
Using cephem antibiotic S-1090, cefcapene, cefdinir, cefpodoxime, and cefditoren, which exhibit different protein binding properties, we evaluated the relationship between therapeutic efficacy against Staphylococcus aureus rat thigh infection models and the concentration at the infection site.
Extracellular free concentrations in the thigh muscle, determined by microdialysis, were significantly smaller than total concentrations in plasma. The free concentration in extracellular muscle fluids was similar to the free concentration in plasma, which was calculated from the total concentration in plasma and rat serum protein binding.
The therapeutic efficacy of CFPN and S-1090 against S. aureus in the rat thigh infection model was determined. The dosage of S-1090 and CFPN, which caused 2 log reduction of viable cells in the thigh muscle compared to the initial inoculum, was 4.73 and 7.16 mg/kg. The time above MIC at these dosages, calculated from extracellular and free concentrations in thigh muscles or free concentrations in plasma, was between 23 and 33%.
These results showed that free concentration in the muscle was as low as the free concentration in plasma, and that S-1090 showed good therapeutic efficacy in rat thigh infection models when T>MIC at infected sites was between 23 and 33%.
Key word
S-1090, microdialysis, tissue concentration, time above MIC, thigh infection model
Received
February 22, 2006
Accepted
June 28, 2006
Jpn. J. Chemother. 54 (5): 440-446, 2006
