Table 1.
Summary of ibrutinib pharmacokinetic parameters after three different treatments using a combination of a single oral and intravenous (i.v.) dose in eight healthy participants
| Mean (SD) | ||||||
|---|---|---|---|---|---|---|
| Oral | i.v. | |||||
| Treatment A | Treatment B | Treatment C | Treatment A | Treatment B | Treatment C | |
| Ibrutinib 560 mg (N = 8) | Ibrutinib 560 mg without GFJ (N = 8) | Ibrutinib 140 mg with GFJ (N = 8) | 13C6PCI‐32 765 100 μg (N = 8) | 13C6PCI‐32 765 100 μg (N = 8) | 13C6PCI‐32 765 100 μg (N = 8) | |
| tmax, h * | 3.75 (0.5–5.02) | 1.77 (1.5–5.0) | 1.5 (1.0–1.5) | 0.03 (0.03–0.08) | 0.03 (0.03–0.1) | 0.03 (0.03–0.08) |
| Cmax, ng ml–1 † | 45.2 (43.3) | 128 (45.6) | 125 (67.5) | 8.54 (5.39) | 8.11 (5.78) | 7.69 (6.29) |
| C0, ng ml–1 † | NA | NA | NA | 40.9 (33.8)† | 25.0 (18.7)† | 26.0 (22.4)§ |
| AUC24, ng h ml–1 § | 229 (107) | 544 (161) | 339 (96.6)† | 1.64 (0.18)‡ | 1.41 (0.35)†, ‡ | 1.44 (0.37)‡ |
| AUClast, ng h ml–1 § | 289 (117) | 606 (160) | 325 (103) | 1.64 (0.18) | 1.41 (0.33) | 1.44 (0.37) |
| AUC∞, ng h ml–1 § | 368 (80.1)§ | 659 (132)† | 334 (105) | 1.64 (0.17)† | 1.36 (0.25)† | 1.47 (0.37) |
| t1/2,term, h | 12.8 (4.90)§ | 9.51 (4.06)† | 5.83 (2.20) | 5.91 (1.38)† | 6.01 (2.21)† | 5.31 (0.80) |
| CL/F, l h–1 | 1572 (318)§ | 875 (144)† | 466 (176) | NA | NA | NA |
| CL, l h–1 | NA | NA | NA | 61.5 (7.00)† | 76.1 (15.6)† | 71.4 (14.2) |
| Vd/F, l | 30 464 (17 148)§ | 12 026 (5783)† | 3757 (1511) | NA | NA | NA |
| Vd, l | NA | NA | NA | 523 (121)† | 683 (375)† | 551 (148) |
AUC24, area under the plasma concentration–time curve from time zero to 24 h; AUC∞, area under the plasma concentration–time curve from time zero to infinite time, calculated as the sum of AUClast and Clast‐‐>/λz; AUClast, area under the plasma concentration–time from time zero to the time of the last quantifiable concentration Clast, the last observed plasma concentration; C0, plasma concentration following i.v. administration, extrapolated back to time zero; CL, total clearance of drug after i.v. administration; CL/F, total clearance of drug after extravascular administration, corrected for F; Cmax, maximum plasma concentration; F, absolute bioavailability; Fg, the fraction escaping the gut; Fh, the fraction escaping first‐pass metabolism in the liver; GFJ, grapefruit juice; NA, not applicable; SD, standard deviation; t1/2, term, terminal half‐life; tmax, time to reach the maximum plasma concentration; Vd, apparent volume of distribution; Vd/F, apparent volume of distribution after extravascular administration, corrected for F.
Median (range);
N = 7;
AUC22;
N = 4.