Overall mean givosiran plasma pharmacokinetic parameters in monkey plasma after administration of a single intravenous bolus or single or multiple subcutaneous dose
| Intravenous | Subcutaneous | ||||
|---|---|---|---|---|---|
| Single dose | Single dose | Multiple dosea | |||
| 10 mg/kg | 1 mg/kg | 5 mg/kg | 10 mg/kg | 1 mg/kg | |
| tmax (h) | — | 1.1 | 2.4 | 1.7 | 1.5 |
| Cmax (µg/ml) | — | 0.133 | 0.830 | 2.14 | 0.136 |
| AUClast (h·µg/ml) | 30.5 | 0.324 | 4.65 | 11.2 | 0.379 |
| t1/2 (h) | 0.2 | 3.2 | 3.5 | 3.5 | 2.8 |
| CL (ml/h per kg) | 340 | — | — | — | — |
| Vss (ml/kg) | 104 | — | — | — | — |
Values represent the overall combined (male + female) mean. n = 6. —, not applicable; tmax, time to reach maximum concentration; Vs, volume of distribution at steady state.
↵aMonkeys were administered givosiran once weekly for a total of eight doses. PK values were determined on day 50.