Plasma OSI-906 pharmacokinetic parameters after single and multiple dosing (twice-daily regimen)
| OSI-906 PK parameters following single oral administration (twice-daily regimen, day 1) | |||||
|---|---|---|---|---|---|
| Dose (mg) | 20 | 40 | 75 | 150 | 200 |
| Evaluable, n | 5 | 3 | 3 | 10 | 3 |
| tmax (h) | 3.0 (2.0–4.0) | 2.0 (1.0–4.0) | 3.0 (2.0–4.0) | 2.1 (1.0–3.2) | 3.0 (1.2–3.2) |
| Cmax (ng/mL) | 242 (121–284) | 401 (395–659) | 762 (629–1,040) | 1,705 (869–3,090) | 2,050 (970–2,990) |
| AUCtau (ng × h/mL) | 830 (366–1,508) | 1,761 (1,093–1,804) | 3,601 (2,437–5,814) | 8,453 (2,557–11,795) | 12,508 (4,668–17,809) |
| AUCinf (ng × h/mL) | 861 (388–1,624) | 1,812 (1,098–1,815) | 4,240 (2,487–6,742) | 9,475 (2,649–12,411) | 9,680a (4,932–14,428) |
| CL/F (L/h) | 23,237 (12,319–51,536) | 22,077 (22,040–36,434) | 17,687 (11,124–30,265) | 15,839 (12,086–56,634) | 27,207a (13,862–40,552) |
| t1/2lambdaz (h) | 2.24 (1.64–3.06) | 1.65 (1.45–1.83) | 3.52 (1.80–4.10) | 2.93 (2.09–4.58) | 3.09 (2.55–6.58) |
| Vz/F (L) | 59,414 (39,865–227,717) | 58,429 (52,490–76,261) | 78,528 (65,576–89,724) | 77,780 (37,730–173,756) | 105,360a (61,701–149,020) |
| OSI-906 PK parameters following multiple oral administrations (twice-daily regimen, day 22) | |||||
| Evaluable, n | 3 | 3 | 3 | 9 | 1 |
| tmax (h) | 2.0 (1.0–8.0) | 3.0 (3.0–4.0) | 6.0 (2.0–12.0) | 2.0 (1.0–3.1) | 1.1 (1.1–1.1) |
| Cmax (ng/mL) | 173 (110–451) | 489 (470–1,290) | 1,420 (944–2,370) | 3,110 (1,190–4,290) | 2,970 (2,970–2,970) |
| AUC0–tau (ng × h/mL) | 846 (616–1,542) | 1,996 (1,577–5,331) | 11,540 (3,408–18,256) | 25,280 (6,967–32,567) | 16,070 (16,070–16,070) |
| AUCinf (ng × h/mL) | 1,117a (645–1,589) | 3,566a (1,590–5,542) | 3,560b (3,560–3,560) | 24,747c (7,588–24,926) | 17,769 (17,669–17,669) |
| CL/F (L/h) | 23,642 (12,974–32,456) | 20,045 (7,503–25,362) | 6,499 (4,108–22,007) | 7,332d (5,425–21,531) | 12,446 (12,466–12,466) |
| t1/2lambdaz (h) | 2.49a (2.33–2.65) | 1.73a (1.35–2.10) | 2.66b (2.66–2.66) | 5.03e (2.93–8.85) | 3.23 (3.23–3.23) |
| Vz/F (L) | 83,741a (43,576–123,907) | 36,052a (22,767–49,336) | 84,306b (84,306–84,306) | 46,793c (44,950–91,032) | 58,058 (58,058–58,058) |
NOTE: Data for all patients who had sufficient pharmacokinetic sampling associated with the OSI-906 doses (pharmacokinetic analysis set).
Abbreviation: tmax, time to reach observed concentration; AUCtau, area under the concentration-time curve during the time interval between consecutive dosing; AUCinf, area under the concentration-time curve from the time of dosing up to infinity with extrapolation of terminal phase; t1/2lambaz, terminal elimination half-life; PK, pharmacokinetic.
↵an = 2; bn = 1; cn = 3; dn = 4; en = 8.