Doripenem Intrapulmonary Pharmacokinetics in Healthy Adult Subjects

• The primary objective is to determine and compare the plasma, epithelial lining fluid, and alveolar macrophages concentrations following multiple intravenous doses of doripenem in healthy, non-smoking adult subjects. [ Time Frame: 32 hours ] [ Designated as safety issue: No ]
  

• The secondary objective of this study is the assessment of safety and tolerability of doripenem as measured by the overall incidence of treatment-emergent adverse events. [ Time Frame: 24 hours post end of doripenem administration ] [ Designated as safety issue: Yes ]
  

The primary objective of this descriptive study is to determine and compare the plasma, epithelial lining fluid (ELF), and alveolar macrophages (AM) concentrations following multiple intravenous doses of doripenem in healthy, non-smoking adult subjects. In brief, each subject who qualifies for the study will be randomized to one of two dosing regimens: doripenem 500 mg or doripenem 1000 mg every 8 hours for a total of three intravenous doses. Each dose of doripenem will be administered as an intravenous infusion over 4 hours. Serial blood samples for determining plasma doripenem concentrations will be collected prior to and after the start of the intravenous infusion of the third doripenem dose. Each subject will undergo one standardized bronchoscopy with BAL in the outpatient bronchoscopy suite at one of four sampling times after the start of the intravenous infusion of the third doripenem dose. BAL collection will provide samples to determine drug concentration in ELF and AM. Safety will be assessed throughout the study by adverse event monitoring, clinical laboratory tests, and vital sign monitoring.