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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 头孢吡普是一种新型头孢菌素头孢吡普的前体药物。 这种抗生素目前正在进行III期临床试验，由于其对革兰氏阳性和革兰氏阴性细菌的活性，是一种非常有前途的一线防御药物，包括耐甲氧西林葡萄球菌属MRSS、耐万古霉素金黄色葡萄球菌VRSA和耐青霉素肺炎链球菌PRSP等耐药菌。 由于该化合物的主要适应症是复杂的皮肤和皮肤结构感染，因此了解感染部位的药物浓度非常重要。这包括软组织，例如皮下脂肪组织和骨骼肌。 FDA和其他监管机构一直在敦促公司更深入地研究药代动力学/药效学关系，以开发最佳给药方案。 为此，必须知道目标部位的药物浓度。 最近，一种新的技术已经成为有用的测量药物浓度在几乎每一个组织，微透析。 本研究的目的是使用微透析技术检查单次静脉输注头孢吡普（500 mg，持续2小时）后的软组织浓度，并与血浆样本进行比较。 本研究是一项非对照、开放标签、研究者发起的研究，将纳入15例受试者，其中3例用于初步研究，12例用于主研究。 将从血浆和软组织中检查以下PK参数：Cmax、tmax、AUClast、AUC、z、t1/2、CL、Vd。此外，AUC组织/AUC血浆浓度比将用于测量组织渗透。

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.