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Medientyp:
E-Artikel
Titel:
Meropenem-RPX7009 Concentrations in Plasma, Epithelial Lining Fluid, and Alveolar Macrophages of Healthy Adult Subjects
Beteiligte:
Wenzler, Eric;
Gotfried, Mark H.;
Loutit, Jeffrey S.;
Durso, Stephanie;
Griffith, David C.;
Dudley, Michael N.;
Rodvold, Keith A.
Erschienen:
American Society for Microbiology, 2015
Erschienen in:
Antimicrobial Agents and Chemotherapy, 59 (2015) 12, Seite 7232-7239
Sprache:
Englisch
DOI:
10.1128/aac.01713-15
ISSN:
0066-4804;
1098-6596
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>ABSTRACT</jats:title><jats:p>The steady-state concentrations of meropenem and the β-lactamase inhibitor RPX7009 in plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) concentrations were obtained in 25 healthy, nonsmoking adult subjects. Subjects received a fixed combination of meropenem (2 g) and RPX7009 (2 g) administered every 8 h, as a 3-h intravenous infusion, for a total of three doses. A bronchoscopy and bronchoalveolar lavage were performed once in each subject at 1.5, 3.25, 4, 6, or 8 h after the start of the last infusion. Meropenem and RPX7009 achieved a similar time course and magnitude of concentrations in plasma and ELF. The mean pharmacokinetic parameters ± the standard deviations of meropenem and RPX7009 determined from serial plasma concentrations were as follows:<jats:italic>C</jats:italic><jats:sub>max</jats:sub>= 58.2 ± 10.8 and 59.0 ± 8.4 μg/ml,<jats:italic>V</jats:italic><jats:sub>ss</jats:sub>= 16.3 ± 2.6 and 17.6 ± 2.6 liters; CL = 11.1 ± 2.1 and 10.1 ± 1.9 liters/h, and<jats:italic>t</jats:italic><jats:sub>1/2</jats:sub>= 1.03 ± 0.15 and 1.27 ± 0.21 h, respectively. The intrapulmonary penetrations of meropenem and RPX7009 were ca. 63 and 53%, respectively, based on the area under the concentration-time curve from 0 to 8 h (AUC<jats:sub>0–8</jats:sub>) values of ELF and total plasma concentrations. When unbound plasma concentrations were considered, ELF penetrations were 65 and 79% for meropenem and RPX7009, respectively. Meropenem concentrations in AMs were below the quantitative limit of detection, whereas median concentrations of RPX7009 in AMs ranged from 2.35 to 6.94 μg/ml. The results from the present study lend support to exploring a fixed combination of meropenem (2 g) and RPX7009 (2 g) for the treatment of lower respiratory tract infections caused by meropenem-resistant Gram-negative pathogens susceptible to the combination of meropenem-RPX7009.</jats:p>