Table 3.
Summary of Lapatinib Pharmacokinetic Parameters in Relation to Lapatinib Dose for Day 1 of Courses 1 and 2
| Variable | Lapatinib Dose (mg/m2) |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 300 |
400 |
520 |
700 |
900 |
||||||
| Median | Range | Median | Range | Median | Range | Median | Range | Median | Range | |
| Course 1, day 1 | ||||||||||
| No. of patients | 5 | 5 | 4 | 12 | 5 | |||||
| Actual dose, mg/m2 | 379 | 313-399 | 457 | 385-532 | 619 | 493-688 | 726 | 379-926 | 921 | 893-987 |
| Cmax, μg/mL | 1.9 | 0.7-2.9 | 2.4 | 1.2-3.9 | 2.1 | 1.3-12.5 | 3.9 | 0.8-6.9 | 4.3 | 1.5-7.5 |
| tmax, hours | 3.0 | 1.5-8.0 | 3.1 | 2.7-7.9 | 3.1 | 3.0-6.0 | 3.3 | 1.5-8.1 | 8.0 | 3.2-8.1 |
| AUC0-12, μg/mL × hours | 12.1 | 5.0-26.2 | 17.3 | 8.7-31.7 | 17.0 | 11.1-75.3 | 31.9 | 7.9-66.7 | 39.2 | 8.3-74.4 |
| 300 | 400 | 500 | 700 | 900 | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Course 2, day 1 | ||||||||||
| No. of patients | 2 | 5 | 2 | 8 | 4 | |||||
| Actual dosage mg/m2 | 324 | 323-326 | 457 | 385-532 | 582 | 507-658 | 707 | 383-813 | 919 | 899-987 |
| Cmax, μg/mL | 2.3 | 1.9-2.7 | 4.1 | 3.1-6.5 | 4.5 | 2.3-6.6 | 7.1 | 2.9-12.1 | 6.2 | 3.1-10.3 |
| tmax, hours | 2.3 | 1.5-3.0 | 3.0 | 1.0-3.2 | 3.3 | 0.5-6.0 | 6.0 | 1.5-8.1 | 5.6 | 3.0-6.2 |
| AUC0-12, μg/mL × hours | 15.2 | 15.2–N/A | 37.5 | 18.1-48.0 | 37.5 | 19.5-55.4 | 70.4 | 28.5-104.3 | 55.2 | 26.2-88.8 |
NOTE. The pharmacokinetic parameters for the two patients studied at the 1,150 mg/m2 dosage level on course 1 day 1 for lapatinib were Cmax = 2.4 and 3.2 μg/mL, tmax = 3.1 and 3.1, and AUC0-12 = 11.5 and 26.7 μg/mL × hours.
Abbreviations: Cmax, maximum plasma concentration; tmax, time to maximum plasma concentration; AUC, area under the [plasma concentration-time] curve; N/A, not available.