Pharmacokinetic variables of sirolimus on day 5, mean ± SD (no. patients)
| Dose group (mg/m2) | Cmax (ng/mL) | tmax (h) | t1/2 (h) | AUC (cycle 1; ng h/mL) | AUC (cycle 3; ng h/mL) | AR | AUCratio | AUCsum (ng h/mL) |
|---|---|---|---|---|---|---|---|---|
| 0.75 | 9.3 ± 4.1 (3) | 25.9* ± 37.5 (3) | 102.0 ± 46.3 (3) | 1,866 ± 1,324 (3) | 1,929 ± 1,132 (2) | 1.8 ± 0.5 (2) | 1.2 ± 0.8 (2) | 3,194 ± 2,603 (2) |
| 1.25 | 27.3 ± 7.6 (3) | 3.6 ± 2.2 (3) | 80.3 ± 15.5 (3) | 4,186 ± 1,293 (3) | 3,688 (1) | 1.3 (1) | 1.7 ± 1.5 (2) | 7,144 ± 182 (2) |
| 2.16 | 34.3 ± 21.2 (5) | 3.6 ± 2.1 (5) | 49.4 ± 27.2 (6) | 3,240 ± 2,463 (6) | 5,309 ± 90 (3) | 1.2 ± 0.4 (3) | 0.9 ± 0.4 (5) | 7,740 ± 2,977 (5) |
| 4.5 | 48.7 ± 16.7 (4) | 2.8 ± 2.3 (4) | 50.3 ± 6.8 (4) | 5,583 ± 2,728 (4) | 4,815 ± 1,488 (3) | 1.1 ± 0.3 (3) | 1.0 ± 0.4 (4) | 10,934 ± 3,384 (4) |
| 15.0 | 57.8 ± 24.3 (5) | 1.8 ± 1.5 (5) | 39.9 ± 1.3 (2) | 4,729 ± 545 (2) | 2,958 (1) | — | 0.6 ± 0.2 (2) | 12,687 ± 4,050 (2) |
| 19.1 | 133.9 ± 70.3 (12) | 2.0 ± 1.5 (12) | 52.3 ± 14.5 (11) | 15,503 ± 8,573 (11) | 11,857 ± 4,724 (4) | 0.5 ± 0.3 (3) | 1.8 ± 1.2 (11) | 2,4781 ± 8,956 (11) |
Abbreviations: AUCratio, uncorrected ratio of sirolimus to temsirolimus AUC; AUCsum, arithmetic sum of temsirolimus and sirolimus AUC.
↵* One of three patients exhibited an abnormally prolonged tmax.