TABLE 4.
Summary table of HTL0009936 exposures in part B (CYP2D6 EM and IM subjects combined), mean (%CV) and [range]
| Dose (mg) a | C mean (ng/mL) b | T max (hr) | C max (ng/mL) | AUC0–24hr (hr.ng/mL) | AUC0‐∞ (hr.ng/mL) | t½ IV (hr) | CLp (L/hr) | CLr (L/hr) |
|---|---|---|---|---|---|---|---|---|
| 13.5 (4.5 + 9) | 27.1 (20) | 1.0 [0.52–5.1] | 33.8 (21) | 192 (27) | 197 (26) | 2.2 (28) | 69 (26) | 8.6 (23) |
| 40 (13.3 + 26.7) | 78.2 (18) | 1.0 [0.58–5.3] | 97.6 (21) | 550 (24) | 564 (24) | 2.3 (33) | 71 (24) | 8.2 (27) |
| 79.5 (26.5 + 53) | 166 (20) | 1.1 [0.83–5.6] | 203 (20) | 1200 (31) c | 1170 (25) | 2.6 (27) | 68 (25) | 7.3 (30) |
Geometric mean and (geometric %CV) except T max median [minimum − maximum] for n = 25–28 observations excluding subjects where infusion was stopped early or interrupted. AUC0‐∞, area under the plasma concentration–time curve from zero extrapolated to infinity; AUC0–24, area under the plasma concentration–time curve from zero to 24 hours post dose; C max, maximum plasma concentration; C mean, mean plasma concentration during 4 hour maintenance infusion; CLp, total plasma clearance; CLr, renal clearance; T max, time to C max; t½ IV, post‐infusion intravenous apparent half‐life;
Loading dose (1 hr at 83.3 mL/hr) + maintenance dose (4 hr at 41.7 mL/hr).
Steady‐state concentration maintained between 1 and 5 hours after the start of dosing.
Includes a subject with a large value of AUC0‐t due to limited available PK sampling times but for whom a value of AUC0‐∞ could not be estimated, therefore the group mean value of AUC0‐t was greater than AUC0‐∞.