Table 2.
Pharmacokinetic parameters in 2‐h IV Infusion and 5‐day IV Infusion of subjects
| Part A (2‐h IV Infusion) | |||||||
|---|---|---|---|---|---|---|---|
| Cmax (ng ml−1) | Tmax (h) | AUC0–t (h.ng ml−1) | AUCinf (h.ng ml−1) | t1/2 (h) | CL (l h−1) | Vz (l) | |
| Panel 1 (1.5 mg h −1 ) (n = 6) | 81.90 (12.4) | 1.5 (1.5–2.0) | 121.90 (13.0) | 180.16 (11.1) | 2.04 (16.2) | 16.59 (12.3) | 72.59 (16.2) |
| Panel 2 (4 mg h −1 ) (n = 6) | 181.89 (16.9) | 2.0 (2.0–2.0) | 233.43 (13.3) | 376.56 (15.9) | 3.95 (30.1) | 21.47 (15.9) | 118.32 (46.0) |
| Panel 3 (10 mg h −1 ) (n = 6) | 504.81 (7.3) | 2.0 (1.0–2.0) | 664.15 (7.31) | 1046.43 (9.0) | 4.68 (21.7) | 19.18 (9.4) | 126.47 (26.8) |
| Panel 4 (25 mg h −1 ) (n = 6) | 1116.28 (42.1) | 2.0 (1.0–2.0) | 1736.70 (22.2) | 2725.14 (23.0) | 4.94 (28.6) | 18.74 (23.2) | 128.79 (35.9) |
| Part B (5‐day IV infusion) | |||||||
|---|---|---|---|---|---|---|---|
| Cmax (ng ml−1) | Tmax (h) | AUC0–t (h.μg ml−1) | AUCinf (h.μg ml−1) | t1/2 (h) | CL (l h−1) | Vz (l) | |
| Panel 5 (1 mg h −1 ) (n = 8) | 58.26 (24.8) | 24 (24–96) | 6.30 (23.1) | 6.38 (23.2) | 6.25 (28.1) | 18.81(25.3) | 188.09 (39.6) |
| Panel 6 (3 mg h −1 ) (n = 8) | 201.58 (21.8) | 60 (4–120) | 21.21 (18.8) | 21.45 (18.9) | 6.22 (14.78) | 16.78 (17.3) | 164.54 (27.3) |
| Panel 7 (9 mg h −1 ) (n = 8) | 520.32 (19.6) | 36 (12–96) | 54.77 (19.4) | 55.54 (19.5) | 8.65 (20.9) | 19.45 (18.6) | 216.06 (29.7) |
| Panel 8 (20 mg h −1 ) (n = 8) | 1170.54 (25.2) | 60 (12–120) | 124.19 (24.6) | 126.02 (24.8) | 7.65 (12.2) | 19.04 (25.9) | 218.90 (28.1) |
Cmax, AUC0‐t, AUCinf, t1/2, CL and Vz are described as geometric mean (CV%); Tmax is described as median (range).
AUC0–t, area under the concentration–time curve for the sampling period; AUCinf, area under the concentration–time curve extrapolated to infinity; CL, clearance; Cmax, maximum plasma concentration; CV%, percentage coefficient of variation; IV, intravenous; t1/2, terminal half‐life; Tmax, time to Cmax; Vz, volume of distribution during the terminal phase