This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. TR-701, an oxazolidinone antibiotic, is a prodrug of the microbiologically-active molecule, TR-700. TR-700 has activity against drug-susceptible and drug-resistant Gram-positive bacteria, and some Gram-negative bacteria such as Legionella pneumophila and the acid-fast bacterium Mycobacterium tuberculosis. Since one of the indications for this compound is complicated skin and skin structure infections, it is important to know the concentration of the drug at the site of infection. This includes subcutaneous adipose tissue and skeletal muscle. Traditionally, however, for lack of an appropriate method to measure the concentration at these sites, plasma samples have been taken to examine the pharmacodynamic response. The FDA and other regulatory agencies have been recommending that companies examine pharmacokinetic/pharmacodynamic relationships more intensely to develop optimal dosing regimens. To do so, the drug concentrations at the target site must be known. Recently, a new sampling technique has become useful in measuring drug concentrations in virtually every tissue, microdialysis.
The aim of this study is to use the microdialysis technique to examine the soft tissue concentrations after a single oral dose of TR-701 compared to plasma samples.
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