Table 4. Summary of pemetrexed pharmacokinetic parameters by dosing cohort arithmetic mean (CV%).
|
Dose (mg m−2) (n)
|
||||||||
|---|---|---|---|---|---|---|---|---|
| Parameter | 300 (3) | 500 (3) | 600 (3) | 700 (6) | 800 (3) | 900 (4) | 1000 (3) | 1200 (6) |
| Dose (mg) | 459 (12.4%) | 783 (7.56%) | 919 (8.28%) | 1180 (8.06%) | 1280 (16.5%) | 1550 (5.47%) | 1820 (7.04%) | 1910 (6.71%) |
| Cmax, (μg ml−1) | 58.2 (7.15%) | 115 (19.1%) | 178 (15.7%) | 172 (9.30%) | 240 (14.5%) | 217 (7.05%) | 269 (17.8%) | 212 (13.2%) |
| AUC0-∞, (μg h ml−1) | 70.1 (7.04%) | 158 (21.6%) | 290 (12.5%) | 250 (23.5%) | 361 (17.0%) | 388 (19.6%) | 382 (6.55%) | 337 (24.6%) |
| CLp (ml min−1) | 109 (5.89%) | 86.5 (32.5%) | 53.0 (3.95%) | 83.4 (27.7%) | 61.4 (35.2%) | 68.5 (20.0%) | 79.3 (2.57%) | 99.7 (24.7%) |
| Vss (l) | 13.5 (22.2%) | 12.1 (20.1%) | 11.5 (25.5%) | 11.7 (20.0%) | 10.6 (33.6%) | 13.9 (31.7%) | 14.4 (7.40%) | 14.8 (9.41%) |
| t1/2 (h) | 2.28 (25.2%) | 2.62 (3.29%) | 3.62 (28.7%) | 2.51 (3.91%) | 2.93 (14.6%) | 3.02 (17.8%) | 2.67 (1.90%) | 2.55 (10.9%) |
| F e | 0.659 (8.78%) | 0.645 (8.34%) | 0.788 (3.76%) | 0.807 (10.1%) | 0.705 (34.9%) | 0.797a (5.11%) | 0.648a (12.5%) | 0.827a (7.58%) |
CV%=coefficient of variation expressed as a percentage; Cmax=maximum observed drug concentration; AUC0-∞=area under the concentration versus time curve from zero to infinity; CL=total body clearance of drug after intravenous administration; Vss=volume of distribution at steady state; t1/2=half-life associated with the terminal rate constant; Fe=fraction of dose eliminated unchanged in urine.
a
The numbers of patients in 900, 1000, and 1200 mgm−2 were three, two, and five, respectively, owing to incompletion of urine collections for patients 209, 210, and 306.