Summary of geometric mean PK parameters of acalabrutinib and total 14C radioactivity in healthy human subjects after 100 mg oral and ≤10 µg intravenous doses
Values are presented as geometric means (%CV) unless otherwise indicated.
| Parameter | Acalabrutinib Oral Dose Cohort 1 (n = 8) | [14C]Acalabrutinib Intravenous Dose Cohort 1 (n = 8)c | Acalabrutinib Plasma Cohort 2 (n = 6) | Total 14Cd | |
|---|---|---|---|---|---|
| Plasma Cohort 2 (n = 6) | Whole Blood Cohort 2 (n = 6) | ||||
| Cmax (ng/ml) | 639 (53.8) | 510 (56.3) | 305 (44.0) | 1340 (34.4) | 1060 (31.3) |
| Tmax (h)a | 0.50 (0.50–0.75) | 0.075 (0.033–0.117) | 0.5 (0.5–0.517) | 0.875 (0.750–2.00) | 0.750 (0.750–2.00) |
| AUC0–t (ng⋅h/ml) | 643 (39.7) | 201 (32.6) | 386 (39.2) | 5930 (29.4) | 11,500 (27.1) |
| AUC0–12 h (ng⋅h/ml) | 642 (35.9) | 199 (30.2) | 406 (36.6) | 4390 (29.4) | 3760 (29.6) |
| AUC0–168 h (ng⋅h/ml) | ND | ND | 407 (36.6) | 6250 (24.9) | 11,500 (27.1) |
| AUC0–∞ (ng⋅h/ml) | 643 (35.7) | 199 (30.2) | 407 (36.6) | 6410 (25.1) | ND |
| t1/2 (h) | 1.57 (0.600) | 1.78 (0.461) | 1.47 (0.45) | 46.5 (21.8) | 395 (9.6)e |
| CL or CL/F (l/h) | 163 (35.7) | 39.4 (30.6) | 246 (36.6) | ND | ND |
| Vz or Vz/F (l) | 344 (36.2) | 98.0 (42.8) | 499 (36.1) | ND | ND |
| Vss (l) | ND | 34.2 (40.2) | ND | ND | ND |
| F (%)b | 25.3 (14.3) | NA | NA | NA | NA |
| Acalabrutinib/total 14C AUC(0–∞) ratio | ND | ND | NA | 0.0635 (17.8) | NA |
| Renal CL (l/h) | 1.21 (32.8) | 0.654 (55.6) | 1.33 (36.0) | ND | ND |
| Cumulative %feu (%) | 0.759 (28.3) | 1.69 (45.7) | 0.519 (56.5) | ND | ND |
%feu, percent excreted in urine over the entire sample collection period; F, bioavailability fraction of dose absorbed relative to intravenous dosing expressed as a percentage; NA, not applicable; ND, not determined; Vss, volume of distribution at steady state; Vz, volume of distribution based on the terminal phase.
↵a Values are the median (minimum–maximum).
↵b Absolute bioavailability was calculated using the dose-normalized AUC0–∞ after oral and intravenous administration due to differing doses with each route of administration, according to the following equation: F = [AUC0–∞ (oral)/AUC0–∞ (intravenous)]/[dose (intravenous)/dose (oral)].
↵c Units are (pg Eq/ml) or (pg Eq⋅h/ml).
↵d Units are (ng Eq/ml) or (ng Eq⋅h/ml).
↵e n = 5. Half-life value is greater than two times the sampling interval.