Table 2.
Renal Classification According to CrCla | |||||
---|---|---|---|---|---|
Normal (n = 6) | Mild (n = 6) | Moderate (n = 6) | Severe (n = 6) | ESRD (n = 6) | |
Plasma parametersb | |||||
AUClast, ng·h/mL | 341.9 (16.5) | 452.9 (32.6) | 650.6 (10.9) | 1244 (24.4) | 1796 (55.5) |
AUC0–inf, ng·h/mL | 358.6 (16.1) | 474.7 (30.0) | 671.6 (11.3) | 1266 (23.6) | 2989 (51.8)c |
Cmax, ng/mL | 73.7 (35.9) | 73.4 (36.8) | 74.8 (20.0) | 109.3 (24.5) | 96.8 (31.9) |
Tmax, h | 1.3 (1.0, 2.0) | 2.0 (1.0, 4.0) | 1.7 (1.0, 5.0) | 2.0 (1.5, 5.0) | 4.0 (1.9, 5.0) |
t1/2, h | 2.8 (36.2) | 3.4 (24.4) | 5.6 (9.5) | 7.5 (14.5) | 39.8 (62.9)c |
CL/F, L/h | 13.9 (16.1) | 10.5 (30.0) | 7.4 (11.3) | 3.9 (23.6) | 1.7 (51.8)c |
Vz/F, L | 56.0 (47.8) | 52.3 (18.1) | 59.8 (19.2) | 42.7 (32.4) | 96.2 (29.1)c |
Urinary parametersb | |||||
Fe0–48 h, % | 75.2 (6.6) | 64.3 (6.8) | 57.0 (10.3) | 46.1 (31.4) | ─ |
CLr, L/h | 10.2 (15.1) | 6.7 (30.0) | 4.3 (8.7) | 1.8 (20.6) | ─ |
AUC0–inf, area under the plasma concentration–time curve up to infinity; AUClast, area under the plasma concentration–time curve up to the last quantifiable time; CL/F, apparent total body clearance; Cmax, maximum plasma concentration; CLr, renal clearance; CrCl, creatinine clearance; CV, coefficient of variance; ESRD, end‐stage renal disease (4‐hour hemodialysis 24 hours after drug administration); Fe0–48 h, cumulative percentage of dose excreted into urine up to 48 hours; Tmax, time to reach maximum plasma concentration; t1/2, terminal elimination half‐life; Vz/F, apparent volume of distribution based on the terminal phase.
Renal function groups, based on the Cockcroft‐Gault formula,12 were normal (estimated creatinine clearance [CrCl] > 80 mL/min/1.73 m2), mild impairment (50 mL/min/1.73 m2 ≤ CrCl ≤ 80 mL/min/1.73 m2), moderate impairment (30 mL/min/1.73 m2 ≤ CrCl < 50 mL/min/1.73 m2), severe impairment (CrCl < 30 mL/min/1.73 m2), and ESRD (patients undergoing hemodialysis, regardless of CrCl).
Geometric mean (geometric CV%) values are presented for parameters excluding Tmax. Median (minimum, maximum) values are presented for Tmax.
n = 5. One subject had 3 unusable PK sampling points.