TABLE 4

Fraction of ISIS 301012 dose excreted (percentage) in urine as ISIS 301012 (parent drug) and its metabolites over the period of 0 to 24 h following intravenous and subcutaneous injection at selected doses compared across species

Parameter
Mouse
Rata
Monkey
Human
Route s.c. Injection s.c. Injection i.v. Bolus 1-h i.v. Infusion 1-h i.v. Infusion 2-h i.v. Infusion 2-h i.v. Infusion
Dose 5 mg/kg 25 mg/kg 5 mg/kg 2 mg/kg 12 mg/kg 50 mg 200 mg
fex, ISIS 301012 1.05 22.2 NM 0.04 2.35 0.91 1.76
fex, metabolites 0 1.5 NM 0.22 0.54 0.47 1.54
fex, total
1.05
23.7
16
0.26
2.89
1.38
3.30

  • fex, fraction of administered dose excreted in urine; NM, not measured.

  • ↵ a Fraction (percentage) of total radiolabel dose excreted in urine.