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Meropenem-RPX7009 Concentrations in Plasma, Epithelial Lining Fluid, and Alveolar Macrophages of Healthy Adult Subjects.
Wenzler, Eric; Gotfried, Mark H; Loutit, Jeffrey S; Durso, Stephanie; Griffith, David C; Dudley, Michael N; Rodvold, Keith A.
Afiliação
  • Wenzler E; College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA.
  • Gotfried MH; Pulmonary Associates, Phoenix, Arizona, USA.
  • Loutit JS; The Medicines Company, San Diego, California, USA.
  • Durso S; The Medicines Company, San Diego, California, USA.
  • Griffith DC; The Medicines Company, San Diego, California, USA.
  • Dudley MN; The Medicines Company, San Diego, California, USA.
  • Rodvold KA; College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA kar@uic.edu.
Antimicrob Agents Chemother ; 59(12): 7232-9, 2015 Dec.
Article em En | MEDLINE | ID: mdl-26349830
The steady-state concentrations of meropenem and the ß-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: Cmax = 58.2 ± 10.8 and 59.0 ± 8.4 µg/ml, Vss = 16.3 ± 2.6 and 17.6 ± 2.6 liters; CL = 11.1 ± 2.1 and 10.1 ± 1.9 liters/h, and t1/2 = 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 (AUC0-8) 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácidos Borônicos / Tienamicinas / Macrófagos Alveolares / Mucosa Respiratória / Compostos Heterocíclicos com 1 Anel / Pulmão / Antibacterianos Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Antimicrob Agents Chemother Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácidos Borônicos / Tienamicinas / Macrófagos Alveolares / Mucosa Respiratória / Compostos Heterocíclicos com 1 Anel / Pulmão / Antibacterianos Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Antimicrob Agents Chemother Ano de publicação: 2015 Tipo de documento: Article