Summary of osimertinib, AZ5104, AZ7550, and plasma and whole blood radioactivity pharmacokinetic parameters in healthy male volunteers after a single oral 20-mg dose of [14C]-osimertinib
| Osimertinib (n = 8) | AZ5104 (n = 8) | AZ7550 (n = 8) | [14C] Plasma (n = 8) | [14C] Blood (n = 8) | ||
|---|---|---|---|---|---|---|
| AUC,a nM⋅h | Geometric mean (geometric CV, %) (range) | 1590 (36.2) (803–2490) | 143 (29.6) (106–242) (n = 7) | 132 (19.9) (92.5–170) (n = 7) | 190,000 (17.7) (153,000–242,000) (n = 7) | 174,000 (12.8) (143,000–219,000) (n = 7) |
| AUC(0–72),a nM⋅h | Geometric mean (range) | 1010 (632–1490) | 72.1 (53.8–108) | 50.9 (40.9–64.0) | 9670 (8060–12,200) | 10,700 (8240–13,200) |
| AUC(0–t),a nM*h | Geometric mean (range) | 1580 (799–2480) | 125 (93.6–234) | 113 (72.3–153) | 178,000 (146,000–227,000) | 158,000 (135,000–206,000) |
| Cmax, nMa | Geometric mean (geometric CV, %) (range) | 29.9 (21.5) (22.3–38.5) | 1.41 (27.3) (0.918–2.09) | 0.957 (17.2) (0.804–1.34) | 217 (15.8) (189–280) | 260 (19.5)(187–330) |
| tmax, h | Median(range) | 6.00 (6.00–8.12) | 6.00 (6.00–36.00) | 36.00 (6.00–48.00) | 144.00 (96.00–168.00) | 132.02 (96.00–168.07) |
| tlag, h | Median(range) | 0.00 (0.00–0.00) | 0.51 (0.50–1.00) | 0.76 (0.00–1.50) | 0.00 (0.00–0.00) | 0.25 (0.00–0.50) |
| t1/2λz, h | Mean(range) | 61.2 (48.2–77.5) | 55.2 (41.3–77.0) | 82.0 (60.2–100) | 474 (415–537) | 562 (477–685) |
| CL/F, liters/h | Mean(range) | 26.7 (16.1–49.9) | N/A | N/A | 0.213 (0.165–0.262) (n = 7) | 0.231 (0.183–0.280) (n = 7) |
| Vz/F, liters | Mean(range) | 2260 (1630–3600) | N/A | N/A | 146 (117–168) (n = 7) | 191 (128–230) (n = 7) |
| MRAUCb | Geometric mean (range) | N/A | 0.0909 (0.0566–0.180) (n = 7) | 0.0848 (0.0635–0.162) (n = 7) | N/A | N/A |
| MRCmaxb | Geometric mean (range) | N/A | 0.0471 (0.0346–0.0937) | 0.0319 (0.0232–0.05502) | N/A | N/A |
| RAUCc | Geometric mean (range) | 0.00826 (0.00429–0.0163) (n = 7) | 0.000751 (0.000508–0.00158) (n = 7) | 0.000698 (0.000566–0.00103) (n = 6) | N/A | 0.917 (0.809–1.06) (n = 7) |
AUC, area under the concentration–time curve; CL/F, apparent total clearance; Cmax, maximum drug concentration; CV, coefficient of variation; N/A, not applicable; t1/2λz, terminal half-life; tlag, lag time; tmax, time to maximum concentration; Vz/F, apparent volume of distribution during terminal phase.
↵a For radioactivity, AUC units are nmol/eq ⋅ h and Cmax units are nmol/eq.
↵b Metabolite (AZ5104 or AZ7550) to parent (osimertinib) ratio of AUC or Cmax.
↵c Ratio of AUC plasma osimertinib, AZ5104, AZ7550, or whole-blood radioactivity to plasma total.