TABLE 1.
Summary of PK parameters in whole blood and plasma following a single 75‐mg oral dose of 14C‐radiolabeled evobrutinib
| Parameter | Evobrutinib | Total radioactivity | |
|---|---|---|---|
| Plasma | Plasma | Whole blood | |
| Cmax, ng (eq)/ml, GM (GM CV, %) a | 321 (33.5) | 1047 (22.8) | 623 (25.5) |
| AUC0–24h, ng (eq) h/ml, GM (GM CV, %) a | 378 (19.4) | 2805 (14.8) | 2001 (9.9) |
| AUC0‐t, ng (eq) h/ml, GM (GM CV, %) a | 375 (19.4) | 3915 (32.7) | 4944 (13.6) |
| T max, h, median (min, max) | 0.50 (0.25, 0.55) | 0.50 (0.25, 1.00) | 0.50 (0.25, 1.00) |
| T 1/2, h, GM (GM CV, %) | 1.33 (27.9) | NC b | NC b |
| CL/F, L/h, GM (GM CV, %) | 199 (19.4) | – | – |
| V z/F, L, GM (GM CV, %) | 381 (33.9) | – | – |
Abbreviations: AUC0‐24, area under the plasma/whole blood concentration–time curve from time zero (dosing) to 24 h after dosing of unchanged drug or radioactivity; AUC0‐t, area under the plasma/whole blood concentration–time curve from time zero (dosing) to the last sampling time at which the concentration is at or above the lower limit of quantification of unchanged drug or radioactivity; CL/F, apparent total body clearance of drug from plasma following oral administration; Cmax, maximum observed concentration of unchanged drug or radioactivity; GM, geometric mean; GM CV, geometric coefficient of variation; NC, not calculated; PK, pharmacokinetic; T max, time to reach the maximum observed concentration of unchanged drug or radioactivity; T 1/2, terminal half‐life of unchanged drug or radioactivity; V z/F, apparent volume of distribution of drug during the terminal phase following oral administration.
ng eq/ml for total radioactivity (by liquid scintillation counting) and ng/mL for evobrutinib (by validated LC‐MS/MS method).
Did not meet acceptable diagnostic criteria.