Table 2.
Mipomersen pharmacokinetic summary from a single and multiple subcutaneous dose-escalation study in healthy human volunteers [26]
| Cohort | 50 mg (A) | 100 mg (B) | 200 mg (C) | 400 mg (D) | ||||
|---|---|---|---|---|---|---|---|---|
| Dose | First | Last | First | Last | First | Last | First | Last |
| n | 3 | 6 | 3 | 3 | 3 | 6 | 4 | 2 |
| AUC(0-48 h) (µg·h/mL) | 7.01 (0.49) | 7.68 (1.8) | 14.5 (2.91) | 19.6 (2.65) | 38.3 (29.8) | 35.4 (8.0) | 106 (17) | 113 |
| C max (µg/mL) | 1.40 (0.29) | 1.0 (0.31) | 1.45 (0.83) | 2.58 (1.41) | 2.73 (1.66) | 2.06 (0.95) | 7.60 (0.81) | 7.15 |
| t max (h) | 2.67 (0.58) | 3.75 (2.23) | 3.00 (1.00) | 3.33 (1.15) | 4.17 (3.40) | 4.64 (3.97) | 4.00 (1.63) | 7.50 |
| Apparent distribution t ½ (h) | 1.84 (0.49) | 3.44 (1.38) | 4.22 (2.71) | 2.96 (1.30) | 3.59 (1.22) | 7.60 (2.13) | 4.33 (0.49) | 5.48 |
| %BAV | 69.2 (9.63) | 77.0 (12.1) | 53.0 (17.2) | 74.5 (4.7) | ||||
Data are presented as mean (standard deviation), except for cohort D at last dose
AUC(0–48 h) area under the plasma concentration–time curve from time zero to 48 h, C max maximum plasma concentration, t max time to reach C max, t ½ terminal elimination half-life, %BAV plasma bioavailability (%) following subcutaneous administration
Adapted from Crooke and Geary [26]