Table 1.
Plasma pharmacokinetic parameter estimates for mipomersen compared across species [27]
| Parameter | Mouse | Rata | Monkey | Human |
|---|---|---|---|---|
| 5 mg/kg SC | 5 mg/kg IV bolus | 4 mg/kg 1-h IV infusion | 200 mg 2-h IV infusion | |
| C max (µg/mL) | 3.8 (0.57) | 73.9 (2.4) | 39.8 (6.7) | 21.5 (4.2) |
| t max (h) | 0.5 | 2 min | 1 (0.1) | 1.98 (0.21) |
| AUC (µg·h/mL) | 7.41 | 27.7 | 82.0 (19.1) | 68.2 (13.5) |
| t ½α (h) | 0.33 | 0.39 | 0.68 (0.19) | 1.26 (0.16) |
| t ½β (day) | NM | 4.7b | 16c | 31.1 (11.4)d |
| CLp (mL/h/kg)e | 674 | 181 | 51.1 (11.1) | 40.9 (5.12) |
| V ss (L/kg)e | NM | 1.0 | 7.7c | 48.3 (14.7)d |
Standard deviation of the estimates is shown in parentheses
Reproduced from Yu et al. [27], with permission
AUC area under the plasma concentration–time curve, C max maximum plasma concentration, CL p plasma clearance, IV intravenous, SC subcutaneous, t max time to reach C max, t ½α distribution half-life, t ½β terminal half-life, V ss apparent volume of distribution at steady state
aMipomersen concentrations were measured using cold a ssay, hybridization ELISA method
bPlasma concentration–time profile seemed triphasic, with a half-life of 2.9 h in the second phase; therefore, this half-life represents the terminal half-life. Additionally, the terminal half-life may be underestimated because of limited time points
c N = 2
dDetermined following SC administration
eCLp/F and Vz/F reported for SC dosing