Table 4.
Noncompartmental Pharmacokinetic Parameters for Erlotinib and OSI-420 in Cycles 1 and 2
| Cycle 1 |
Cycle 2 |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parameter* (units) |
Arm A | n¥ | Arm B | n | Total | n | Arm A | n | Arm B | n | Total | n |
| Erlotinib (OSI-774) | ||||||||||||
| AUC0-24** (mg/L*hr) |
15.3 (7.5–35.8) |
13 | 12.4 (3.4–31.6) |
12 | 12.6 (3.4–35.8) |
25 | 26.3 (8.9–51.0) |
14 | 21.4 (1.4–71.5) |
10 | 22.9 (1.4–71.5) |
24 |
| Cmax£ (mg/L) |
0.91 (0.32–2.1) |
13 | 0.79 (0.16–1.9) |
12 | 0.88 (0.16–2.1) |
25 | 1.7 (0.48–3.2) |
14 | 1.6 (0.28–3.1) |
10 | 1.6 (0.28–3.2) |
24 |
| CL/F§ (L/hr) |
9.8 (4.2–20.1) |
13 | 13.5 (5.5–44.5) |
12 | 12.3 (4.2–44.5) |
25 | 5.7 (2.9–16.8) |
14 | 7.6 (2.1–110) |
10 | 6.6 (2.1–110) |
24 |
| Tmax† (hrs) |
5 (1–24) |
13 | 4 (1–8) |
12 | 4 (1–24) |
25 | 2 (1–6) |
14 | 2.5 (0–10) |
10 | 2 (0–10) |
24 |
| T1/2‡ (hrs) |
11.6 (2.1–116) |
11 | 11.2 (4.7–29.9) |
9 | 11.6 (2.1–116) |
20 | 28.4 (5.7–68.5) |
14 | 19.7 (1.7–45.6) |
7 | 22.5 (1.7–68.5) |
21 |
| OSI-420ƛ | ||||||||||||
| AUC0-24 (mg/L*hr) |
0.93 (0.088–4.5) |
13 | 0.69 (0–1.7) |
11 | 0.87 (0–4.5) |
24 | 1.4 (0.19–10.7) |
14 | 1.7 (0–6.9) |
9 | 1.5 (0–10.7) |
23 |
| AUC Ratio€ 420/774 |
0.068 (0.004–0.129) |
13 | 0.056 (0–0.109) |
11 | 0.066 (0–0.127) |
24 | 0.102 (0.011–0.209) |
14 | 0.094 (0–0.149) |
9 | 0.096 (0–0.209) |
23 |
| Cmax (mg/L) |
0.070 (0.010–0.203) |
13 | 0.048 (0–0.119) |
11 | 0.054 (0–0.203) |
24 | 0.100 (0.009–0.558) |
14 | 0.178 (0–0.412) |
9 | 0.153 (0–0.558) |
23 |
| Tmax (hrs) |
5 (1–24) |
13 | 2 (1–11.4) |
11 | 4 (1–24) |
24 | 2 (0–10) |
14 | 2.5 (1–6) |
9 | 2 (0–10) |
23 |
| T1/2 (hrs) |
9.6 (7–70.4) |
8 | 12.3 (3.2–40.8) |
6 | 9.7 (3.2–70.4) |
14 | 22.2 (6–71.1) |
10 | 17.7 (3.4–28.8) |
6 | 22.2 (3.4–71.1) |
16 |
*
Data are presented as median (range).
**
AUC, area under the observed concentration vs. time curve;
£
Cmax, maximum observed concentration;
§
CL/F, apparent clearance/oral bioavailability (F);
†
Tmax, time of observed maximum concentration;
‡
T1/2, terminal phase half-life (note half-lives were too long to be determined for some patients);
¥
n, the number of concentration vs. time profiles used for each median value;
€
AUC Ratio, the ratio of AUCs calculated as (AUC OSI-420)/(AUC OSI-774).
ƛ
OSI-420 was undetectable in one patient treated on Arm B