CLINICAL TRIAL: EXPLORATORY STUDY TO EVALUATE PENETRATION OF CEFTOBIPROLE INTO S

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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. Ceftobiprole medocaril is the prodrug of the new, novel cephalosporin, ceftobiprole. This antibiotic is currently undergoing phase III clinical trials and is a very promising agent for a first line defense due to its activity against both Gram-positive and Gram-negative bacteria, including resistant species such as methicillin-resistant Staphylococcus species MRSS, vancomycin-resistant Staphylococcus aureus VRSA, and penicillin-resistant Streptococcus pneumoniae PRSP. Since the lead indication of 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 soft tissues such as subcutaneous adipose tissue and skeletal muscle. The FDA and other regulatory agencies have been urging companies to 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 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 exam the soft tissue concentrations after a single IV infusion of ceftobiprole, 500 mg over 2 hours, compared to plasma samples. The study is a non-controlled, open-label, investigator initiated which will include 15 subjects, 3 for the pilot study and 12 for the main study. The following PK parameters will be examined from plasma and the soft tissues; Cmax, tmax, AUClast, AUC, z, t1/2, CL, Vd. Also AUC tissue/AUC plasma concentration ratios will be used to measure tissue penetration.