Human Vss after intravenous dosing and estimates of human Vss from tissue composition approaches
Scenario 1: Rodgers and Rowland method (using BPR to estimate acidic phospholipid affinity) (Rodgers et al., 2005a); scenario 2: Poulin and Theil method (Poulin and Theil, 2000); scenario 3: Poulin and Theil method using the modifications suggested by Berezhkovskiy (2004); and scenario 4: Rodgers and Rowland method using SPR data to estimate acidic phospholipid affinity.
| Compound | Vss | Predicted Vss | |||
|---|---|---|---|---|---|
| Scenario 1 | Scenario 2 | Scenario 3 | Scenario 4 | ||
| l/kg | l/kg | ||||
| Amlodipine | 17 | 8.1 | 3.4 | 3.3 | 31.9 |
| Propranolol | 3.1 | 1.3 | 2.8 | 2.3 | 4.0 |
| UK-390957 | 5.2a | 25.5b | 2.9 | 1.6 | 3.9 |
| AAFE | 2.9 | 2.1 | 2.8 | 1.5 | |
a Vss for UK-390957 was 398 ± 75 liters (mean ± S.D.; n = 15 individuals); mean body weight for the individuals was 76.7 kg.
b A blood/plasma concentration ratio of 3.5 was used in the calculation because plasma concentrations were <100 ng/ml in the clinical study with UK-390957.