TABLE 5.

Pharmacokinetic parameters of CXA-101 after multiple intravenous infusions

ParameteraStatisticbValue in cohort
500 mg q8h (n = 6)1,000 mg q8h (n = 6)1,500 mg q12h (n = 6)
Day 1Day 10Day 1Day 10Day 1Day 10
C max (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)
T max (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)
V ss (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)
T 1/2 (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)NAc304.3 (9)NA304.6 (12.2)NA471.3 (5.9)
Median (range)NA309.8 (264.4-334.6)NA310.6 (253-341.6)NA479.4 (422.9-497.1)
Accumulation indexMean (% CV)NA1.092 (3.5)NA1.155 (7.2)NA1.03 (0.5)
Median (range)NA1.099 (1.046-1.134)NA1.123 (1.079-1.289)NA1.029 (1.024-1.038)
  • a C max, 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.