Schaadt R D, Batts D H, Daley-Yates P T, Pawsey S D, Stalker D J, Zurenko G E
Infectious Diseases Research, Pharmacia & Upjohn, Inc., Kalamazoo, Michigan 49001, USA.
Diagn Microbiol Infect Dis. 1997 Aug;28(4):201-4. doi: 10.1016/s0732-8893(97)00071-0.
In Phase I trials subjects received multiple doses of eperezolid (PNU-100592; formerly U-100592) and linezolid (PNU-100766; formerly U-100766), and steady-state samples were drawn at the projected peak and trough timepoints. Serum inhibitory titer and serum bactericidal titer values were determined using single strains of Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pneumoniae. Serum inhibitory titer values generally correlated with drug concentration in serum and inherent organism susceptibility. Against S. aureus and E. faecalis sera from patients dosed with either drug were generally inhibitory at the peak timepoint, but at trough only linezolid exhibited a persistent effect. No bactericidal activity was seen for either drug against S. aureus or E. faecalis. The sera from patients dosed with either drug exhibited inhibition of S. pneumoniae at peak and trough. Bactericidal activity was seen against S. pneumoniae for both drugs at peak time and at trough for many of the sera for patients on the higher dose regimens. The results demonstrated that the sera from most human subjects dosed with eperezolid or linezolid were inhibitory to S. aureus and E. faecalis and S. pneumoniae and that many of the samples exhibited bactericidal activity for S. pneumoniae.
在I期试验中，受试者接受了多次剂量的依哌唑胺（PNU - 100592；原U - 100592）和利奈唑胺（PNU - 100766；原U - 100766），并在预计的峰浓度和谷浓度时间点采集稳态样本。使用金黄色葡萄球菌、粪肠球菌和肺炎链球菌的单一菌株测定血清抑菌滴度和血清杀菌滴度值。血清抑菌滴度值通常与血清中的药物浓度和固有菌株敏感性相关。对于金黄色葡萄球菌和粪肠球菌，接受这两种药物治疗的患者血清在峰浓度时间点通常具有抑菌作用，但在谷浓度时只有利奈唑胺表现出持续的作用。两种药物对金黄色葡萄球菌或粪肠球菌均未观察到杀菌活性。接受这两种药物治疗的患者血清在峰浓度和谷浓度时均表现出对肺炎链球菌的抑制作用。对于接受高剂量方案治疗的患者，许多血清样本在峰浓度时以及谷浓度时对肺炎链球菌均显示出杀菌活性。结果表明，大多数接受依哌唑胺或利奈唑胺治疗的人类受试者血清对金黄色葡萄球菌、粪肠球菌和肺炎链球菌具有抑制作用，并且许多样本对肺炎链球菌具有杀菌活性。
