Table 2. Mean pharmacokinetic parameters of temsirolimus and sirolimus in whole blood.
|
Temsirolimus, mean (CV)
|
Sirolimus, mean (CV)
|
|||
|---|---|---|---|---|
| Pharmacokinetic parameter | Temsirolimus (5 mg) | Temsirolimus (5 mg)+ ketoconazole (400 mg) | Temsirolimus (5 mg) | Temsirolimus (5 mg)+ ketoconazole (400 mg) |
| Cmax (ng ml−1) | 278.3 (5.8%) | 262.6 (15.5%) | 13.3 (27.4%) | 29.0 (13.6%) |
| Tmax (h) | 0.5 (0) | 0.5 (0) | 3.3 (37.7%) | 3.0 (0) |
| T1/2 (h) | 22.3 (19.6%) | 23.7 (17.0%) | 74.8 (10.8%) | 112.8 (18.1%) |
| AUCT (h ng ml−1) | 873.4 (11.9%) | 969.1 (15.0%) | 918.3 (28.3%) | 2410.7 (22.0%) |
| AUC (h ng ml−1) | 885.5 (11.7%) | 991.6 (14.5%) | 1204.7 (30.2%) | 3888.9 (29.2%) |
| CL2 (l h−1) | 5.7 (11.0%) | 5.1 (13.8%) | 4.5 (28.6%) | 1.4 (32.7%) |
| Vz3 (l) | 182.0 (17.1%) | 173.6 (16.4%) | 479.7 (27.5%) | 220.4 (24.5%) |
| Vss4 (l) | 86.8 (14.6%) | 91.5 (17.5%) | 493.6 (25.4%) | 227.1 (22.0%) |
| AUCratio | 1.35 (23.9%) | 3.94 (28.0%) | ||
| AUCsum (h ng ml−1) | 2090 (21.0%) | 4881 (25.0%) | ||
AUC=area under the concentration curve; AUCsum=sum of temsirolimus plus sirolimus AUC; AUCT=area under the concentration–time curve; CL=clearance; Cmax=maximum concentration; T1/2=half-life; Tmax=time to reach Cmax; Vz=apparent volume of distribution during the terminal phase; Vss=steady-state volume of distribution.
2
For sirolimus=CL/fm (l h−1).
3
For sirolimus=Vz/fm (l).
4
For sirolimus=Vss/fm (l).