Table 3.
Summary of pharmacokinetic parameters in healthy subjects administered a single subcutaneous dose of pasireotide 2.5–1200 μg
| Dose (μg) | n | tmax (h) | Cmax (ng/mL) | AUClast (ng · h/mL) | AUC∞ (ng · h/mL) | CL/F (L/h) | t½,α (h) | t½,β (h) | t½,γ (h) | Vz/F (L) |
|---|---|---|---|---|---|---|---|---|---|---|
| 2.5 | 6 | 0.25 (0.25–0.50) | 0.06 ± 0.01 | 0.11 ± 0.09 | NA* | NA* | 2.6 ± 1.4 | NA* | NA* | NA* |
| 10 | 6 | 0.25 (0.25–0.25) | 0.24 ± 0.06 | 0.66 ± 0.25 | NA* | NA* | 2.0 ± 0.5 | NA* | NA* | 38.1 ± 0.0 |
| 30 | 6 | 0.25 (0.25–0.50) | 0.72 ± 0.17 | 2.78 ± 1.02 | NA* | NA* | 2.2 ± 0.8 | 7.4 ± 2.2 | NA* | 105.0 ± 5.7 |
| 100 | 8 | 0.50 (0.25–0.50) | 2.23 ± 0.45 | 9.10 ± 2.37 | 9.59 ± 2.44 | 11.00 ± 2.67 | 1.6 ± 0.3 | 8.1 ± 1.4 | NA* | 131.0 ± 41.0 |
| 200 | 4 | 0.38 (0.25–1.00) | 3.73 ± 0.90 | 16.8 ± 3.65 | 17.5 ± 3.82 | 11.90 ± 2.56 | 1.7 ± 0.6 | 7.8 ± 2.1 | NA* | 161.5 ± 33.9 |
| 300 | 6 | 0.38 (0.25–1.50) | 4.71 ± 1.79 | 26.0 ± 6.87 | 27.1 ± 6.98 | 11.9 ± 3.88 | 2.4 ± 0.7 | 10.7 ± 1.0 | NA* | 180.5 ± 44.3 |
| 600 | 6 | 0.50 (0.25–1.00) | 15.6 ± 3.25 | 75.6 ± 11.2 | 78.6 ± 12.3 | 7.82 ± 1.39 | 2.2 ± 0.6 | 9.1 ± 5.2 | 31.7 ± 6.5 | 464.0 ± 439.6 |
| 1200 | 6 | 0.50 (0.50–1.00) | 22.2 ± 5.53 | 90.4 ± 13.2 | 93.6 ± 13.6 | 13.1 ± 2.09 | 1.7± 0.4 | 9.1 ± 2.1 | 65.8 ± 69.5 | 1190.0 ± 1572.3 |
Notes:
*
Not applicable due to limited data points in the terminal phase or the number of subjects with available parameters was less than 50% of the total enrolled subjects in this cohort. Data are median (range) for tmax and mean ± standard deviation for all others. At the lowest dose of 1 μg, pasireotide concentrations were below the LLOQ (0.03 ng/mL). For the doses between 2.5 and 30 μg, only a partial concentration versus time profile was detected (around 2–5 hours post-dose).
Abbreviations: AUC, area under the concentration–time curve; CL/F, apparent total body clearance; LLOQ, lower limit of quantification.