Table 3.
Pharmacokinetic parameters following cocaine infusion (10 mg, IV).
| Study Day 3a | Study Day 11 | |||
|---|---|---|---|---|
| Parameter | Nepicastat 0 mg (n = 13) |
Placebo (n = 3) |
Nepicastat 160 mg (n = 13) |
Placebo (n = 3) |
| Cmax [ng/mL] | ||||
| Mean (SD) | 97.97 (46.48) | 86.20 (18.57) | 75.37 (29.35) | 62.80 (23.11) |
| Median | 93.40 | 94.00 | 70 | 65 |
| CV (%) | 47 | 22 | 39 | 37 |
| AUC0–last [min * ng/mL] | ||||
| Mean (SD) | 5080 (2437) | 4607 (1351) | 3975 (807) | 3931 (1365) |
| Median | 4867 | 4778 | 4196 | 3691 |
| CV (%) | 48 | 29 | 20 | 35 |
| AUC∞ [min * ng/mL] | ||||
| Mean (SD) | 5469 (2439) | 5033 (1412) | 4361 (846) | 4192 (1416) |
| Median | 5180 | 5135 | 4540 | 3977 |
| CV (%) | 45 | 28 | 19 | 34 |
| T1/2 [min] | ||||
| Mean (SD) | 81.9 (23.6) | 91.6 (35.1) | 80.7 (37.0) | 66.6 (13.8) |
| Median | 76.9 | 82.5 | 70.3 | 70.7 |
| CV (%) | 29 | 38 | 46 | 21 |
| Clearance [mL/min] | ||||
| Mean (SD) | 2068 (652) | 2104 (632) | 2387 (530) | 2574 (852) |
| Median | 1930 | 1947 | 2202 | 2515 |
| CV (%) | 32 | 30 | 22 | 33 |
| Volume of distribution [L] | ||||
| Mean (SD) | 234.6 (75.7) | 258.8 (32.1) | 267.5 (99.0) | 236.2 (34.0) |
| Median | 211.9 | 250.5 | 226.8 | 255.2 |
| CV (%) | 32 | 12 | 37 | 14 |
Abbreviations: AUC, area under the curve; Cmax, maximum concentration; CV, coefficient of variability (= standard deviation / mean); SD, standard deviation; T1/2, apparent half-life.
a
The nepicastat group (n = 13) was dosed with placebo from Study Day 1 to 4.