Article Figures & Data
Figures
- FIG 1
Mean (± the SD) concentration-versus-time profile of meropenem and RPX7009 in plasma (A) and epithelial lining fluid (B) before and after the third dose meropenem (2 g) and RPX7009 (2 g) administered as a 3-h i.v. infusion. In plate A, meropenem is illustrated by the filled circles and a solid line, and RPX7009 is illustrated by open circles and a dashed line. In plate B, meropenem is illustrated by the filled triangles and a solid line, and RPX7009 is illustrated by open triangles and a dashed line. Shaded region represents the 3-h infusion period. The y axis is in the log scale.
- FIG 2
Individual concentrations of meropenem in plasma (A; ●) and epithelial lining fluid (ELF) (B; ▲) and RPX7009 in plasma (C; ○) and ELF (D; △) at 1.5, 3.25, 4, 6, and 8 h after the third dose of meropenem (2 g) and RPX7009 (2 g) administered as a 3-h i.v. infusion. The shaded region represents the 3-h infusion period. Solid and dashed lines represent the median concentrations in plasma and ELF, respectively. The y axis is in the log scale.
- FIG 3
Individual concentrations of RPX7009 in alveolar macrophages (AM) (open squares) at 1.5, 3.25, 4, 6, and 8 h after the third dose of meropenem (2 g) and RPX7009 (2 g) administered as a 3-h i.v. infusion. The shaded region represents the 3-h infusion period. The solid line represents the median concentration in AM. The y axis is in the log scale.
- FIG 4
Mean (± the SD) plasma (● and ○; solid line) and epithelial lining fluid (ELF) (▲ and △; dashed lines) concentration-versus-time profiles of meropenem (A) and RPX7009 (B) at 1.5, 3.25, 4, 6, and 8 h after the third dose of meropenem (2 g) and RPX7009 (2 g) administered as a 3-h i.v. infusion. The shaded region represents the 3-h infusion period. The y axis is in the log scale.
Tables
- TABLE 1
Characteristics of healthy adult subjects receiving meropenem and RPX7009
Subject category No. of male subjects (%) Mean ± SD Age (yr) Ht (cm) Wt (kg) CLCR (ml/min)a Total cell count in BAL fluid (cells/mm3) Macrophages (%) All subjects (n = 25) 18 (72) 39.0 ± 10.6 173.9 ± 9.5 80.3 ± 9.4 93.9 ± 22.8 141.1 ± 100.8 85.4 ± 9.2 BAL sampling time (h)b 1.5 5 (100) 32.2 ± 8.9 180.9 ± 7.0 83.2 ± 5.5 113.1 ± 12.5 113.6 ± 46.3 89.4 ± 7.0 3.25 3 (60) 39.6 ± 11.5 173.6 ± 10.3 80.5 ± 11.9 86.5 ± 15.1 92.2 ± 52.3 82.6 ± 13.1 4 5 (100) 40.4 ± 9.4 178.6 ± 10.1 80.8 ± 13 105.7 ± 34.8 172.6 ± 80.4 91.0 ± 4.0 6 3 (60) 43.0 ± 12.4 168.5 ± 9.1 80.9 ± 8.3 84.8 ± 19.5 197.2 ± 186.1 79.6 ± 9.7 8 2 (40) 39.8 ± 11.8 168.1 ± 5.2 76.2 ± 9.2 79.3 ± 8.9 129.8 ± 76.0 84.6 ± 7.9 - TABLE 2
Pharmacokinetic parameters of meropenem (2 g) and RPX (2 g) in plasma infused over 3 h
Treatment Mean ± SD Cmax (μg/ml) AUC0–8 (μg·h/ml) Vss (liters) CL (liters/h) t1/2 (h) Meropenem 58.2 ± 10.8 186 ± 33.6 16.3 ± 2.6 11.1 ± 2.1 1.03 ± 0.15 RPX7009 59.0 ± 8.4 204 ± 34.6 17.6 ± 2.6 10.1 ± 1.9 1.27 ± 0.21 - TABLE 3
Meropenem concentrations in plasma (total), epithelial lining fluid, and alveolar macrophages at sampling time of bronchoscopy and bronchoalveolar lavagea
BAL sampling time (h) Mean concn (μg/ml) ± SD of meropenem in: Total plasma ELF AM 1.5 41.2 ± 5.02 21.4 ± 3.96 BQL 3.25 47.7 ± 7.28 28.3 ± 6.69 BQL 4 23.8 ± 4.30 16.1 ± 4.77 BQL 6 7.24 ± 2.79 7.51 ± 5.29 BQL 8 1.36 ± 0.51 2.51 ± 1.13 BQL ↵a ELF, epithelial lining fluid; AM, alveolar macrophages; BAL, bronchoalveolar lavage; BQL, below the quantitative limit of detection (0.01 μg/ml).
- TABLE 4
RPX7009 concentrations in plasma (total), epithelial lining fluid, and alveolar macrophages at sampling time of bronchoscopy and bronchoalveolar lavagea
BAL sampling time (h) Mean concn ± SD or median concn (range) of RPX7009 in μg/ml in: Total plasma ELF AM 1.5 42.1 ± 5.00 18.6 ± 3.76 2.28 (1.29–4.69) 3.25 51.1 ± 6.78 26.1 ± 7.12 4.68 (2.08–25.1) 4 28.2 ± 5.32 15.7 ± 3.36 6.94 (1.26–8.36) 6 10.8 ± 2.82 8.04 ± 5.81 3.85 (2.32–95.9) 8 2.74 ± 1.12 2.61 ± 1.35 2.35 (2.22–11.7) ↵a ELF, epithelial lining fluid; AM, alveolar macrophages; BAL, bronchoalveolar lavage.
