Table 1.
Summary of the Pharmacokinetic Parameters for SMT C1100 Following Single Oral Doses and Multiple Doses. Geometric Mean (Coefficient of Variation) Are Presented Unless Otherwise Stated
| Parameter | Single‐Dose Study | Multiple‐Dose Study | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 50 mg/kg (n = 6) | 100 mg/kg (n = 6) | 200 mg/kg (n = 6) | 400 mg/kg (n = 6) | 200 mg/kg Fasted (n = 5) | 100 mg/kg (n = 6) | 200 mg/kg (n = 6) | |||||
| Day 1 | Day 7 | Day 10 | Day 1 | Day 7 | Day 10 | ||||||
| AUC0‐∞ a | 1612 | 2932 | 2766 | 4215 | 492 | – | – | – | – | – | |
| (ng · h/mL) | (47.0) | (79.9) | (89.0) | (125) | (222) d | ||||||
| AUC0‐ τ | – | – | – | – | – | 1980 | 1343 | 1469 | 1390 | 1001 | 830 |
| (ng · h/mL) | (38.3) | (59.1) | (63.6) | (54.9) | (46.1) | (53.3) | |||||
| Cmax (ng/mL) | 226 (41.5) | 383 (88.2) | 373 (71.8) | 531 (103) | 73.0 (103) | 316 (40.0) | 203 (56.8) | 218 (66.8) | 255 (50.1) | 150 (45.2) | 122 (52.8) |
| tmax (hour) b | 2 (1–3) | 2.5 (0.5–3.02) | 3 (0.5–3) | 3.5 (2–4) | 2 (0.5–3) | 2.5 (1–3) | 3 (2–4) | 3 (2–4) | 2.5 (2–3) | 3 (2–4.02) | 3.53 (2–4) |
| t½ (hour) | 20.6 (42.2) | 22.6 (21.1) | 19.9 (73.6) | 19.8 (38.7) | 12.8 (246) d | – | – | 35.7 (29.8) | – | – | 29.0 (31.3) |
| CL/F (mL/min/kg) | 517 (47.0) | 569 (79.9) | 1205 (89.0) | 1582 (125) | 6768 (222) d | – | 1234 (67.3) c | 1134 (63.6) | – | 3330 (46.1) | 4014 (53.3) |
| Vz/F (L/kg) | 922 (35.3) | 1112 (73.0) | 2078 (19.6) | 2711 (139) | 7494 (37.3) d | 235 (30.7) | 475 (53.6) | 3510 (91.0) | 608 (47.3) | 1357 (32.9) | 10089 (54.1) |
| RAobs | – | – | – | – | 0.704 (25.0) | 0.770 (28.0) | – | 0.720 (29.9) | 0.597 (36.4) | ||
AUC0‐∞ = area under the plasma concentration‐time curve from time zero to infinity (percentage of AUC that is due to extrapolation from tz to infinity was <10% in all cases); AUC0− τ = area under the plasma concentration‐time curve over a dosing interval; Cmax = maximum observed plasma concentration; tmax = time of maximum observed plasma concentration; t½ = apparent plasma terminal elimination half‐life (for Day 10 of multiple‐dose study this is post drug induction); CL/F = apparent total plasma clearance; VZ/F = apparent volume of distribution during the terminal phase; RAobs = observed accumulation ratio based on AUC0‐ τ.
Arithmetic mean (CV%).
Median (min–max).
n = 5.
n = 3.