Table 4.

Plasma OSI-906 pharmacokinetic parameters after single dosing (once-daily regimen, day 1)

Dose (mg)10204075150300400450
Evaluable, n63433464
tmax (h)2.5 (1.0–10.0)2.0 (1.0–4.0)2.5 (2.0–4.0)3.0 (0.8–4.0)3.0 (2.0–6.1)3.1 (2.0–8.0)3.0 (1.9–24)3.6 (3.0–6.0)
Cmax (ng/mL)76.6 (44.8–1,120)171 (74.1–192)420 (354–1,620)1,040 (538–1,260)1,440 (1,380–1,670)2,725 (1,490–6,710)2,905 (594–4,160)5,415 (3,020–10,200)
AUCtau (ng × h/mL)223a (205–630)630 (523–777)1,874 (1,687–7,992)4,621 (4,193–4,990)9,811 (4,922–12,063)26,527 (95,556–48,525)22,258 (3,440–51,005)50,574 (26,440–82,550)
AUCinf (ng × h/mL)223a (201–635)599 (541–7,590)1,887 (1,694–8,059)4,649 (4,265–50,780)10,083 (4,879–12,327)27,944 (5,504–48,675)16,485 (3,677–27,742)60,403 (26,880–91,663)
CL/F (L/h)44,789a (15,757–9,639)33,397 (26,363–36,962)21,306 (4,963–23,609)16,131 (14,678–7,583)14,876 (12,169–30,745)10,736 (6,163–54,509)24,448 (14,418–108,784)7,450 (4,909–16,741)
t1/2lambdaz (h)2.20a (1.11–3.22)2.22 (2.20–2.41)3.10 (2.56–3.72)3.64 (2.97–4.28)3.85 (1.35–4.23)2.53 (1.15–5.16)3.52 (2.35–5.09)6.91 (3.62–8.65)
Vz/F (L)104,055a (71,740–150,546)106,897 (83,750–128,718)85,173 (23,923–122,544)91,204 (69,123–92,359)67,587 (60,094–90,737)79,933 (22,498–90,122)92,471 (79,733–798,673)87,411 (48,955–92,930)

NOTE: Data for all patients who had sufficient pharmacokinetic sampling associated with the OSI-906 doses (pharmacokinetic analysis set).

Abbreviations: 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; NC, not calculated.