Pharmacokinetic summary: multiple 1-h i.v. ISIS 104838 infusions (mean ± S.D.)
| Dose | N | Cmax at EOI | AUC | Plasma Clearance | Vss | MRT | Effective Plasmat1/2eff | Terminal Eliminationt1/2 |
|---|---|---|---|---|---|---|---|---|
| mg/kg | mg/ml | mg · h/ml | ml/h/kg | ml/kg | h | days | ||
| 0.1 | 3 | 0.8 (±0.2) | 0.9 (±0.3) | 122.0 (±31.6) | 65.5 (±12.7) | 0.53 (±0.04) | 0.37 (±0.03) | Not tested |
| 0.5 | 3 | 5.3 (±0.9) | 9.0 (±2.6) | 58.8 (±15.5) | 75.8 (±6.6) | 1.22 (±0.36) | 0.84 (±0.25) | Not tested |
| 1.0 | 3 | 10.2 (±0.9) | 20.3 (±2.9) | 49.9 (±7.2) | 98.9 (±31.0) | 1.41 (±1.03) | 0.97 (±0.11) | Not tested |
| 2.0 (obese) | 2 | 39.6 (36.3, 42.8) | 85.9 (76.5, 95.3) | 23.6 (21.0, 26.1) | 105.0 (55, 155) | 2.13 (1.91, 2.34) | 1.48 (1.32, 1.63) | Not tested |
| 2.0 | 3 | 25.9 (±5.3) | 49.0 (±5.4) | 41.2 (±4.8) | 162.0 (±22.4) | 2.10 (±0.18) | 1.46 (±0.12) | 11.9 (±4.0) |
| 4.0 | 3 | 41.1 (±6.3) | 91.9 (±13.1) | 44.1 (±6.2) | 293.0 (±114) | 2.48 (±0.07) | 1.71 (±0.05) | 13.0 (±2.6) |
| 6.0 | 3 | 52.5 (±9.4) | 117.0 (±5.7) | 52.5 (±9.4) | 184.0 (±46.0) | 2.63 (±0.42) | 1.82 (±0.29) | 27.0 (±3.8) |
V ss, volume of distribution at steady-state; t 1/2eff, effective plasma half-life.