Plasma pharmacokinetic parameter estimates for ISIS 301012 compared across species
Standard deviation of the estimates is shown in parentheses.
Parameter | Mouse | Rata | Monkey | Human |
|---|---|---|---|---|
| Dose and route | 5 mg/kg s.c. | 5 mg/kg i.v. bolus | 4 mg/kg 1-h i.v. infusion | 200 mg 2-h i.v. infusion |
| Cmax (μg/ml) | 3.8 (0.57) | 73.9 (2.4) | 39.8 (6.7) | 21.5 (4.2) |
| Tmax (h) | 0.5 | 2 min | 1 (0) | 1.98 (0.21) |
| AUC (μg · h/ml) | 7.41 | 27.7 | 82.0 (19.1) | 68.2 (13.5) |
| t1/2α (h) | 0.33 | 0.39 | 0.68 (0.19) | 1.26 (0.16) |
| t1/2β (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) |
| Vss (l/kg)e | NM | 1.0 | 7.7c | 48.3 (14.7)d |
↵ a ISIS 301012 concentrations were measured using cold assay, hybridization ELISA method.
↵ b Plasma concentration-time profile seemed triphasic, with a half-life of 2.9 h in the second phase; thus, this half-life represents the terminal half-life. Additionally, the terminal half-life may be underestimated because of limited time points.
↵ c n = 2.
↵ d Determined following s.c. administration.
↵ e CLp/F and Vz/F reported for s.c. dosing.