Table 2.
Primary and secondary pharmacokinetic parameters for XM17
| PK parameter | Statistic | 37.5 IU (n=4) |
75 IU (n=12) |
150 IU (n=12) |
300 IU (n=12) |
|---|---|---|---|---|---|
| Cmax (pre-dose corrected) in IU/L | Ncalc | 4 | 12 | 12 | 12 |
| Mean (SD) | 2.085 (1.019) | 2.329 (0.953) | 4.420 (0.652) | 9.835 (2.355) | |
| Geometric mean | 1.886 | 2.155 | 4.376 | 9.547 | |
| Median | 2.005 | 2.215 | 4.340 | 10.275 | |
| Min–max | 0.93–3.40 | 1.10–4.38 | 3.27–5.59 | 5.59–14.01 | |
| AUC0–168h (IU·h/L)a | Ncalc | 2 | 12 | 12 | 11 |
| Mean (SD) | 125.05 (141.35) | 204.24 (95.27) | 359.44 (75.69) | 792.05 (112.36) | |
| Geometric mean | 75.15 | 174.54 | 352.77 | 784.25 | |
| Median | 125.05 | 222.55 | 339.05 | 829.90 | |
| Min–max | 25.1–225.0 | 32.2–339.4 | 286.9–513.8 | 597.3–939.4 | |
| AUC0–t (IU·h/L) | Ncalc | 4 | 12 | 12 | 12 |
| Mean (SD) | 185.93 (113.87) | 204.35 (95.36) | 359.32 (75.69) | 839.04 (194.57) | |
| Geometric mean | 135.45 | 174.42 | 352.63 | 820.94 | |
| Median | 212.70 | 222.45 | 339.55 | 830.50 | |
| Min–max | 25.5–292.8 | 31.6–340.8 | 286.8–513.8 | 598.8–1,355.5 | |
| AUC0–∞ (IU·h/L) | Ncalc | 1 | 9 | 12 | 11 |
| Mean (SD) | 65.20 | 298.29 (202.61) | 448.20 (135.75) | 1,345.25 (809.14) | |
| Geometric mean | 65.20 | 222.01 | 430.35 | 1,203.26 | |
| Median | 65.20 | 267.20 | 414.75 | 1,023.50 | |
| Min–max | 65.2–65.2 | 38.3–579.7 | 297.6–687.1 | 628.9–3,599.9 | |
| λZ (1/hour)b | Ncalc | 1 | 9 | 12 | 11 |
| Mean (SD) | 0.0097 | 0.0108 (0.0062) | 0.0146 (0.0087) | 0.0102 (0.0071) | |
| Geometric mean | 0.0097 | 0.0095 | 0.0128 | 0.0077 | |
| Median | 0.0097 | 0.0102 | 0.0111 | 0.0090 | |
| Min–max | 0.0097–0.0097 | 0.0044–0.0243 | 0.0074–0.0368 | 0.0017–0.0215 | |
| VZ/F (L) | Ncalc | 1 | 9 | 12 | 11 |
| Mean (SD) | 59.2 | 41.4 (30.0) | 28.3 (8.0) | 36.1 (17.6) | |
| Geometric mean | 59.2 | 35.7 | 27.2 | 32.4 | |
| Median | 59.2 | 29.2 | 28.6 | 34.1 | |
| Min–max | 59.2–59.2 | 20.7–118.3 | 13.6–43.7 | 16.2–74.0 | |
| tmax (hours) | Ncalc | 4 | 12 | 12 | 12 |
| Mean (SD) | 122.4 (75.8) | 53.9 (64.4) | 22.1 (11.1) | 30.4 (35.9) | |
| Geometric mean | 79.8 | 30.6 | 19.7 | 22.9 | |
| Median | 155.8 | 24.0 | 24.0 | 24.0 | |
| Min–max | 10.0–168.0 | 10.0–168.3 | 10.0–47.6 | 10.1–143.2 | |
| t1/2 (hours) | Ncalc | 1 | 9 | 12 | 11 |
| Mean (SD) | 71.4 | 82.2 (40.7) | 60.2 (26.1) | 127.4 (120.1) | |
| Geometric mean | 71.4 | 73.1 | 54.1 | 90.1 | |
| Median | 71.4 | 67.6 | 63.2 | 77.0 | |
| Min–max | 71.4–71.4 | 28.6–156.6 | 18.9–93.7 | 32.3–408.4 | |
| CL/F (L/hour) | Ncalc | 1 | 9 | 12 | 11 |
| Mean (SD) | 0.575 | 0.520 (0.600) | 0.362 (0.102) | 0.270 (0.102) | |
| Geometric mean | 0.575 | 0.338 | 0.349 | 0.249 | |
| Median | 0.575 | 0.281 | 0.363 | 0.293 | |
| Min–max | 0.575–0.575 | 0.129–1.960 | 0.218–0.504 | 0.083–0.477 |
Notes:
Not evaluable in three subjects (two in the 37.5 IU group and one in the 300 IU group) because samples were taken earlier than scheduled at last time point;
in three subjects in the 37.5 IU group, three in the 75 IU group, and one in the 300 IU group, the λZ or any PK parameters derived from λZ were not estimable because an exponential decline over at least three data points could not be determined by inspection.
Abbreviations: IU, international unit; n, number of subjects within group; Ncalc, number of subjects used for calculation; L, litre; h, hour; SD, standard deviation; Cmax, maximum XM17 concentration; AUC0–168h, area under the XM17 concentration-time curve from time zero to 168 hours post-dose; AUC0–t, area under the XM17 concentration-time curve from time zero to the time of last observed concentration; AUC0–∞, area under the XM17 concentration time-curve from time zero to infinity; λZ, apparent terminal rate constant; Vz/F, apparent volume of distribution; tmax, time at which Cmax occurred; t1/2, apparent terminal elimination half-life; CL/F, apparent clearance.