Table 4.

Summary of pharmacokinetic parameter following single (day 1) and multiple dosing (days 5 and 7) of OSI-906 (S2 and S3)

Treatment schedule, day/OSI-906 dose (mg)
S2, Day 1S3, Day 1S2, Day 5S3, Day 7
450450600450450600
Evaluable, n4310437
tmax, h6.0 (2.1–12.0)8.0 (6.0–12.2)4.0 (2.0–24.0)3.4 (2.9–4.0)3.0 (2.0–4.1)3.0 (2.0–6.1)
Cmax, μg/mL3.08 (1.17–5.60)2.78 (2.49–3.62)4.55 (0.572–10.9)3.45 (1.25–10.0)4.75 (2.83–5.74)4.11 (2.11–9.78)
AUCtau, μg × h/mL24.3 (13.3–52.7)25.5 (22.1–26.4)46.6 (5.58–182)31.8 (10.9–108)26.2 (17.7–35.9)28.8 (21.0–113)
AUCinf, μg × h/mL25.5 (13.4–54.6)25.9 (22.4–26.6)50.7a (19.3–89.9)33.3 (11.2–115)26.3 (17.9–36.0)30.8b (21.1–119)
CL/F, L/h17.7 (8.24–33.6)17.4 (16.9–20.1)11.8a (6.67–31.1)18.0 (3.90–40.4)17.1 (12.5–25.2)19.6b (5.04–28.4)
t1/2λz, h3.40 (2.24–5.78)2.57 (2.40–2.79)4.06 (2.20–22.8)4.91 (3.97–6.55)2.54 (2.46–3.47)3.44 (2.65–14.3)
Vz/F, L88.5 (49.0–149)68.1 (60.2–74.5)72.0a (43.1–101)144 (30.6–255)62.8 (44.4–126)96.8b (34.9–252)

Abbreviations: AUCinf, area under the concentration-time curve from the time of dosing up to infinity with extrapolation of terminal phase; AUCtau, area under the concentration time curve during dosing interval; CL/F, apparent body clearance after extravascular dosing; Cmax, maximum plasma concentration; s, schedule; t1/2λz, terminal elimination half-life; tmax, median time to reach observed concentration; Vz/F, volume of distribution.

  • an = 7; bn = 6.