TABLE 3.
Summary of the pharmacokinetic parameters of probe drugs administered alone and with zanubrutinib 160 mg b.i.d.
| Probe drug | Parameter (unit) | Probe drugs only | Probe drugs + zanubrutinib 160 mg b.i.d. | Ratio of GLSM (%) | 90% CI (%) | ||
|---|---|---|---|---|---|---|---|
| n | Mean (cv%) | n | Mean (cv%) | ||||
| S‐warfarin | AUC0‐t (h*ng/mL) | 18 | 18 150 (35.17) | 16 | 18 040 (18.76) | 99.8 | 97.41–102.2 |
| AUC0‐∞ (h*ng/mL) | 16 | 19 150 (19.73) | 16 | 19 220 (19.58) | 100.4 | 97.92–102.9 | |
| Cmax (ng/mL) | 18 | 698 (14.9) | 16 | 666 (22.2) | 95.25 | 87.6–104.0 | |
| Tmax (h)a | 18 | 1.00 (0.500–4.00) | 16 | 1.00 (0.500–2.00) | — | — | |
| t1/2 (h)b | 18 | 39.3 (18.5) | 16 | 34.3 (3.71) | — | — | |
| Midazolam | AUC0‐t (h*ng/mL) | 18 | 26.93 (42.27) | 17 | 14.27 (35.44) | 52.52 | 48.49–56.88 |
| AUC0‐∞ (h*ng/mL) | 18 | 28.22 (43.64) | 17 | 14.97 (36.23) | 52.58 | 48.50–57.02 | |
| Cmax (ng/mL) | 18 | 10.2 (28.7) | 17 | 7.12 (35.6) | 70.17 | 63.20–77.91 | |
| Tmax (h)a | 18 | 0.500 (0.500–1.03) | 17 | 0.500 (0.500–1.00) | — | — | |
| t1/2 (h)b | 18 | 4.87 (2.29) | 17 | 2.51 (0.653) | — | — | |
| Digoxin | AUC0‐t (h*pg/mL) | 17 | 6544 (19.21) | 17 | 7281 (20.11) | 111.3 | 103.8–119.3 |
| Cmax (pg/mL) | 17 | 1160 (33.1) | 17 | 1560 (43.2) | 134.1 | 116.1–154.8 | |
| Tmax (h)a | 17 | 1.00 (0.500–2.00) | 17 | 1.00 (0.500–2.00) | — | — | |
| Rosuvastatin | AUC0‐t (h*ng/mL) | 17 | 36.79 (44.65) | 17 | 32.90 (37.38) | 89.45 | 78.73–101.6 |
| AUC0‐∞ (h*ng/mL) | 15 | 40.98 (42.72) | 15 | 34.39 (36.84) | 89.29 | 79.15–100.7 | |
| Cmax (ng/mL) | 17 | 3.47 (62.5) | 17 | 3.75 (47.6) | 108 | 91.92–127.0 | |
| Tmax (h)a | 17 | 3.00 (2.00–8.00) | 17 | 3.00 (1.50–4.05) | — | — | |
| t1/2 (h)b | 15 | 12.9 (4.28) | 15 | 11.2 (4.42) | — | — | |
| Omeprazole | AUC0‐t (h*ng/mL) | 16 | 451.8 (74.32) | 15 | 282.2 (90.92) | 63.52 | 57.40–70.30 |
| Cmax (ng/mL) | 17 | 229 (63.4) | 17 | 182 (78.4) | 79.5 | 64.97–97.28 | |
| Tmax (h)a | 17 | 2.00 (1.00–8.00) | 17 | 2.00 (1.50–4.00) | — | — | |
Abbreviations: AUC0‐∞ = area under the concentration‐time curve from time zero to infinity; AUC0‐t = area under the concentration–time curve from time zero to the time of the last quantifiable concentration; b.i.d. = twice daily; CI = confidence interval; C max = maximum observed plasma concentration; CV = coefficient of variation; GLSM = geometric least squares mean; t 1/2 = apparent terminal elimination half‐life; T max = time of the maximum observed plasma concentration.
Note: Geometric mean (CV%) data are presented;
a
Median (min‐max) data are provided for T max;
b
Arithmetic mean (SD) data are provided for t 1/2.