Cendejas-Bueno E, Forastiero A, Ruiz I, Mellado E, Gavaldà J, Gomez-Lopez A
Instituto de Salud Carlos III, Madrid, 28220, Spain; Clinical Microbiology Department, Hospital Universitario La Paz, Madrid, 28046, Spain.
Instituto de Salud Carlos III, Madrid, 28220, Spain.
Diagn Microbiol Infect Dis. 2017 Feb;87(2):112-117. doi: 10.1016/j.diagmicrobio.2016.10.010. Epub 2016 Oct 11.
Posaconazole is the recommended prophylactic agent in patients at high risk of invasive fungal infection, since adequate drug levels seem to be reached in target sites despite the relatively low levels detected in blood. The objective of this study is to obtain pharmacokinetic (PK) information associated to blood and tissue distribution of posaconazole in an animal model of invasive pulmonary aspergillosis. The PK parameters in lung samples were systematically higher than in serum. After multiple-dose administration of posaconazole, a significant accumulation of the drug was evident in lung tissue. The PK behavior of posaconazole in this particular experimental model is similar to that observed in humans. Thus, we believe this model could be a valid tool to evaluate posaconazole exposure-response relationship.
泊沙康唑是侵袭性真菌感染高危患者的推荐预防用药，因为尽管血液中检测到的药物水平相对较低，但在靶部位似乎能达到足够的药物水平。本研究的目的是在侵袭性肺曲霉病动物模型中获取与泊沙康唑血液和组织分布相关的药代动力学（PK）信息。肺样本中的PK参数系统性地高于血清中的参数。多次给药泊沙康唑后，肺组织中明显有药物大量蓄积。泊沙康唑在这个特定实验模型中的PK行为与在人类中观察到的相似。因此，我们认为这个模型可能是评估泊沙康唑暴露-反应关系的有效工具。
