TABLE 4.

Pharmacokinetic parameters of CXA-101 after single ascending doses

ParameteraStatisticbValue in cohort
250 mg (n = 6)500 mg (n = 6)1,000 mg (n = 6)1,500 mg (n = 6)2,000 mg (n = 6)
C max (μg/ml)Mean (% CV)16.5 (15.6)32.2 (12.1)58.4 (31.5)87.4 (8)127.7 (11.8)
Median (range)15.8 (13.6-20.3)31.9 (28.1-37.4)57.8 (42.1-92.9)89.5 (76.9-94.4)126.9 (114-150)
T max (h)Mean (% CV)1.03 (4.1)1.03 (2.7)1.05 (3.8)1.03 (3.8)1.06 (7)
Median (range)1.01 (1-1.09)1.02 (1.01-1.08)1.05 (1.01-1.09)1.02 (1-1.08)1.04 (1-1.16)
AUC0-∞ (h·μg/ml)Mean (% CV)40.1 (8.5)84.1 (14.4)152.1 (19.7)242.8 (8.3)344.2 (22.5)
Median (range)41.3 (36.2-44.4)80.9 (75.4-108)142.5 (129.9-207.2)245.7 (216.7-263.6)332.2 (277.6-470.8)
CL (ml/min)Mean (% CV)103.9 (8.5)99.1 (14.4)109.6 (19.7)103 (8.3)96.9 (22.5)
Median (range)100.9 (93.8-115)103.1 (77.2-110.6)116.9 (80.5-128.3)101.8 (94.9-115.4)100.4 (70.8-120.1)
CLR (ml/min)Mean (% CV)100.9 (11)90.4 (16.8)93.4 (47.6)96.2 (6.6)92.9 (29.9)
Median (range)100.4 (87.1-120.1)96.6 (69.5-105.2)103.4 (43.5-130.6)98.6 (86-102.2)94 (68.3-123.6)
V ss (liter)Mean (% CV)13.1 (14.9)14.8 (22)16.3 (25.5)17.6 (12.3)14.8 (9.2)
Median (range)13.7 (10.5-15)15.5 (11.1-18.6)16.5 (11-20.8)17.8 (15.4-20.8)14.4 (13.1-16.7)
T 1/2 (h)Mean (% CV)1.86 (9.9)2.34 (35.4)2.25 (16.2)2.62 (13.8)2.45 (22.5)
Median (range)1.86 (1.63-2.06)2.35 (1.71-3.88)2.27 (1.82-2.68)2.5 (2.29-3.14)2.54 (1.85-2.98)
MRT (h)Mean (% CV)2.09 (11.2)2.5 (31)2.48 (13.3)2.85 (9.1)2.54 (22.9)
Median (range)2.05 (1.87-2.37)2.48 (1.91-4.01)2.53 (2.03-2.86)2.83 (2.57-3.25)2.59 (1.97-3.42)
Urinary recovery in 24 h (% of dose)Mean (% CV)97.1 (7.9)91.2 (4.5)85.2 (26.4)93.4 (6.1)97.7 (5.2)
Median (range)98.9 (85.8-104.8)90.6 (85.3-96.3)91 (54.1-104)93.9 (85.6-102.5)98.3 (91.5-102.9)
  • 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.