i.v. Dose | AUCnorm | Clp | Clb 1-b | t1/2 | VdSS | |
---|---|---|---|---|---|---|
mg/kg | μg · min · kg/mg · ml | ml/min/kg | ml/min/kg | h | l/kg | |
Rats | 0.2 (N = 3) | 20.0 ± 4.51-a | 52.0 ± 13.7 | 26 | NC | NC |
3 (N = 3) | 16.2 ± 0.9 | 61.7 ± 3.4 | 31 | 8.1 ± 0.2 | 22.7 ± 2.3 | |
3 (N = 3)1-c | 24.5 ± 6.0 | 42.8 ± 12.0 | 22 | 11.5 ± 3.2 | 16.9 ± 6.6 | |
Dogs | 3 (N = 3) | 51.5 ± 5.8 | 19.6 ± 2.1 | 10 | 14.0 ± 3.0 | 12.0 ± 1.1 |
Monkeys | 0.3 (N = 3)1-d | 44.3 ± 4.7 | 22.8 ± 2.3 | 11 | NC | NC |
3 (N = 3)1-e | 54.5 ± 11.8 | 19.0 ± 4.6 | 10 | 9.0 ± 0.9 | 6.2 ± 1.8 |
p.v. Dose | AUCnorm | Eh | ||||
---|---|---|---|---|---|---|
mg/kg | μg · min · kg/mg · ml | % | ||||
Rats | 0.2 (N = 2) | 14.0 ± 1.0 | 30 | |||
Monkeys | 0.3 (N = 4)1-e | 23.7 ± 3.3 | 47 |
Oral Dose | AUCnorm | Cmax | Tmax | F | ||
---|---|---|---|---|---|---|
mg/kg | μg · min · kg/mg · ml | μg/ml | h | % | ||
Rats | 10 (N = 3) | 2.7 ± 0.9 | 0.126 ± 0.082 | 2.0 ± 0.0 | 17 ± 6 | |
10 (N = 3)1-c | 4.8 ± 1.7 | 0.091 ± 0.023 | 4.0 ± 0.0 | 19 ± 7 | ||
Dogs | 10 (N = 5) | 10.8 ± 3.0 | 0.150 ± 0.032 | 3.4 ± 2.4 | 27 ± 8 | |
Monkeys | 10 (N = 2)1-e | 2.0 ± 0.1 | 0.032 ± 0.005 | 3.0 ± 1.4 | 4 ± 1 | |
10 (N = 3)1-d | 2.0 ± 0.1 | 0.035 ± 0.018 | 4.0 ± 2.0 | 5 ± 2 |
Clb, blood (systemic) clearance; p.v., portal vein; NC, not calculated.
↵1-a Values represent mean ± S.D.
↵1-b Blood clearance [calculated by dividingClp by the blood-to-plasma ratio (Cb/Cp = 2)].
↵1-c Data from study in bile duct-cannulated rats.
↵1-d Data from 3-period crossover study to evaluate hepatic extraction in monkeys.
↵1-e Results from initial 2-period crossover study in monkeys; one animal did not receive complete oral dose.