Table 3.
Summary of geometric mean (SD) pharmacokinetic parameters of HMS5552
| Parameters | HMS5552 (N=48)a
|
|||||
|---|---|---|---|---|---|---|
| 5 mg (n=8) | 10 mg (n=8) | 15 mg (n=8) | 25 mg (n=8) | 35 mg (n=8) | 50 mg (n=8) | |
| Cmax (ng/mL) | 62.6 (11.4) | 119.0 (26.9) | 204.0 (41.5) | 350.0 (65.2) | 418.0 (68.1) | 582.0 (202) |
| Tmax (h)b | 1.75 (0.46) | 2.25 (0.99) | 1.50 (1.24) | 2.50 (1.58) | 2.00 (1.07) | 1.25 (1.77) |
| AUC0–t (ng⋅h/mL) | 405 (84.5) | 857 (140) | 1,261 (4,349) | 2,124 (644) | 2,653 (193) | 3,969 (1,314) |
| AUC0–∞ (ng⋅h/mL) | 413 (86.6) | 867 (141) | 1,268 (351) | 2,135 (646) | 2,665 (192) | 3,979 (1,316) |
| t1/2 (h) | 4.48 (1.05) | 6.37 (3.08) | 5.41 (1.07) | 6.94 (1.16) | 7.51 (3.15) | 6.34 (2.11) |
| V/f (L) | 78.3 (15.9) | 106 (51.7) | 92.4 (36.8) | 117 (44.5) | 142 (53.3) | 115 (41.0) |
| CL/f (L/h) | 12.1 (2.79) | 11.5 (1.96) | 11.8 (3.59) | 11.7 (3.65) | 13.1 (0.98) | 12.6 (5.87) |
| Ae0–72 (mg) | 0.44 (0.06) | 0.79 (0.24) | 1.29 (0.44) | 2.07 (0.97) | 3.24 (0.37) | 5.24 (0.97) |
| fe0–72 (%) | 8.85 (1.28) | 7.90 (2.40) | 8.57 (2.91) | 8.29 (3.89) | 9.25 (1.05) | 10.48 (1.94) |
Notes: N, total number of subjects; n, number of subjects in each group.
Four males and four females per group except the 50 mg group (five males and three females).
Median (SD).
Abbreviations: SD, standard deviation; Cmax, maximum plasma concentration; Tmax, time to reach maximum plasma concentration; AUC0–t, area under the curve 0 to the last quantifiable concentration; AUC0–∞, area under the curve from 0 to infinity; t1/2, terminal elimination half-life; V/f, volume of apparent distribution during the terminal phase; CL/f, apparent total plasma clearance; Ae0–72, amount of drug excreted in urine from 0 to 72 hours; fe0–72, fraction of unchanged dose excreted in urine from 0 to 72 hours.