Table 1.
Summary of plasma pyrotinib, SHR150980, SHR151468, SHR151136, and radioactivity pharmacokinetic parameters in six healthy male volunteers after a single oral 402-mg dose of [14C]pyrotinib
| Radioactivity | Pyrotinib | SHR150980 | SHR151468 | SHR151136 | ||
|---|---|---|---|---|---|---|
| AUC0–∞ h × ng eq./mL | Geometric mean (Geometric CV, %) (range) | 18200 (25.7) (13200–26300) | 1970 (18.9) (1510–2500) | 352 (33.3) (210–510) | 179 (30.5) (124–284) | 553 (20.2) (463–783) |
| AUC0–last h × ng eq./mL | Geometric mean (Geometric CV, %) (range) | 12900 (34.0) (8220–18400) | 1940 (18.9) (1490–2470) | 339 (34.5) (199–504) | 173 (30.9) (119–276) | 546 (19.9) (457–769) |
| AUC0–48 h h × ng eq./mL | Geometric mean (Geometric CV, %) (range) | 9020 (13.8) (7670–11100) | 1730 (19.3) (1340–2290) | 292 (33.3) (174–458) | 170 (29.7) (119–276) | 533 (20.6) (457–769) |
| Cmax ng eq./mL | Geometric mean (Geometric CV, %) (range) | 396 (27.2) (296–557) | 99.0 (22.3) (85.1–151) | 16.3 (38.2) (8.96–28.6) | 10.2 (36.8) (5.70–17.2) | 43.6 (26.9) (32.8–69.1) |
| tmax, h | Mean (range) | 3.7 (3.0–5.0) | 4.5 (3.0–5.0) | 3.7 (3.0–5.0) | 4.3 (3.0–8.0) | 3.5 (3.0–5.0) |
| t1/2, h | Mean (range) | 47.9 (25.5–76.2) | 29.3 (17.0–39.2) | 32.2 (16.3–55.3) | 10.4 (8.1–13.4) | 9.75 (7.1–11.7) |
| CL/F, liters/h | Mean (range) | 22.7 (15.3–30.5) | 207 (161–266) | N/A | N/A | N/A |
| Vz/F, liters | Mean (range) | 1460 (1120–1720) | 8570 (4370–107000) | N/A | N/A | N/A |
| RAUC, 0–48 h%a | Geometric mean (range) | N/A | 19.2 (14.8–22.9) | 3.2 (2.3–4.6) | 1.9 (1.6–2.8) | 5.9 (5.1–7.7) |
| RAUC, 0–∞ %a | Geometric mean (range) | N/A | 10.9 (9.5–11.8) | 1.9 (1.1–2.5) | 1.0 (0.6–1.2) | 3.0 (2.6–3.5) |
AUC area under the concentration-time curve, CL/F apparent total clearance, Cmax maximum drug concentration, CV coefficient of variation, N/A not applicable, t1/2 terminal half-life, tmax time to maximum concentration, Vz/F apparent volume of distribution during terminal phase
aRatio of AUC0–48 h or AUC0–∞ plasma pyrotinib, SHR150980, SHR151468, and SHR151136 to total plasma radioactivity