TABLE 5.
Pharmacokinetic parameters of CXA-101 after multiple intravenous infusions
| Parametera | Statisticb | Value in cohort |
|||||
|---|---|---|---|---|---|---|---|
| 500 mg q8h (n = 6) |
1,000 mg q8h (n = 6) |
1,500 mg q12h (n = 6) |
|||||
| Day 1 | Day 10 | Day 1 | Day 10 | Day 1 | Day 10 | ||
| Cmax (μg/ml) | Mean (% CV) | 34.3 (9) | 33.3 (15.9) | 52.8 (23.7) | 58 (10.3) | 85.4 (15.2) | 82.6 (15.9) |
| Median (range) | 33.3 (31.8-38.5) | 34.8 (25.6-37.8) | 53.3 (39.8-65.2) | 58.8 (48.1-64) | 89.1 (67.3-102) | 87.7 (67.1-93.8) | |
| Tmax (h) | Mean (% CV) | 1.03 (2.6) | 0.93 (24.1) | 1.03 (4.1) | 1.05 (9.1) | 1.03 (4) | 1 (0.2) |
| Median (range) | 1.03 (1-1.06) | 1.01 (0.6-1.08) | 1 (1-1.08) | 1.02 (1-1.25) | 1 (1-1.08) | 1 (1-1.01) | |
| AUC0-∞ (h·μg/ml) | Mean (% CV) | 88.1 (14.1) | 82.9 (20.6) | 148.6 (18.2) | 143.3 (15.4) | 219 (20) | 207 (15.9) |
| Median (range) | 84.7 (79.7-110.9) | 82.5 (61.5-104.7) | 155.3 (108.9-178.2) | 145.8 (115.5-173) | 243.1 (163.2-250) | 220.1 (166.5-240.6) | |
| CL (ml/min) | Mean (% CV) | 94.6 (14.1) | 100.6 (20.6) | 112.1 (18.2) | 116.4 (15.4) | 114.2 (20) | 120.8 (15.9) |
| Median (range) | 98.4 (75.2-104.5) | 101.1 (79.6-135.6) | 107.3 (93.6-153.1) | 114.3 (96.3-144.3) | 102.8 (100-153.2) | 113.6 (103.9-150.2) | |
| CLR (ml/min) | Mean (% CV) | 78.4 (34.2) | 87.6 (21.8) | 111.5 (13.4) | 111.2 (16.4) | 118.9 (26.9) | 127.2 (17.4) |
| Median (range) | 84.6 (57.7-113) | 84.6 (69.1-109.8) | 113.4 (92.4-133.2) | 110.6 (89-131) | 109.6 (91.3-176.9) | 125.7 (99.6-162.1) | |
| Vss (liter) | Mean (% CV) | 13.8 (7.2) | 14 (19.6) | 17.8 (21.5) | 17.1 (13.7) | 18.1 (13.8) | 18.1 (14.2) |
| Median (range) | 13.6 (13-15.5) | 13.4 (11.2-18.8) | 17.6 (14.5-23.4) | 17.6 (14.3-19.7) | 17.6 (15.3-21.6) | 17.5 (15.7-21.7) | |
| T1/2 (h) | Mean (% CV) | 2.21 (14.8) | 2.2 (17.7) | 2.38 (15.1) | 2.69 (24) | 2.72 (12.9) | 2.34 (4.9) |
| Median (range) | 2.22 (1.76-2.52) | 2.3 (1.78-2.6) | 2.36 (1.97-2.86) | 2.5 (2.12-3.71) | 2.76 (2.25-3.16) | 2.32 (2.22-2.52) | |
| MRT (h) | Mean (% CV) | 2.42 (15.9) | 2.32 (13.4) | 2.64 (13.4) | 2.45 (14) | 2.64 (11.7) | 2.5 (7.2) |
| Median (range) | 2.25 (2.1-3.02) | 2.36 (1.94-2.72) | 2.58 (2.27-3.3) | 2.39 (2.07-2.96) | 2.7 (2.2-3.03) | 2.45 (2.38-2.87) | |
| Urinary recovery (% of dose) | Mean (% CV) | 82.9 (25) | 84.6 (21.7) | 99.4 (8.1) | 94.1 (4) | 104.1 (8.9) | 105.3 (7.6) |
| Median (range) | 87.3 (59.4-108.1) | 81 (64.1-106.3) | 100.7 (87-107.2) | 92.4 (90.8-98.5) | 105.5 (89.4-115.5) | 106.5 (95.8-117) | |
| Fluctuation % | Mean (% CV) | NAc | 304.3 (9) | NA | 304.6 (12.2) | NA | 471.3 (5.9) |
| Median (range) | NA | 309.8 (264.4-334.6) | NA | 310.6 (253-341.6) | NA | 479.4 (422.9-497.1) | |
| Accumulation index | Mean (% CV) | NA | 1.092 (3.5) | NA | 1.155 (7.2) | NA | 1.03 (0.5) |
| Median (range) | NA | 1.099 (1.046-1.134) | NA | 1.123 (1.079-1.289) | NA | 1.029 (1.024-1.038) | |
a
Cmax, maximum plasma concentration; Tmax, time of maximum plasma concentration; AUC0-∞, area under the concentration-time curve from zero hour to infinity; CL, clearance; CLR, renal clearance; Vss, volume of distribution at steady state; T1/2, half-life in plasma.
b
CV, coefficient of variation.
c
NA, not applicable.