Parameter | Wild Type | Oct1/2 Knockout |
---|---|---|
Intravenous dose, mg/kga | 10 | 10 |
AUC0-t, μg · h/ml | 2.41 | 9.10 |
AUC0-∞, μg · h/ml | 2.84 | 9.84 |
C0, μg/ml | 22.7 | 67.4 |
CL, ml · min−1 · kg−1 | 58.7 | 16.9 |
Vd,ss, ml/kg | 1520 | 318 |
T1/2, h | 0.31 | 0.20 |
Urinary excretion, % doseb | 35 ± 4 | 30 ± 6 |
Creatinine renal CL, ml/min | 0.09 ± 0.01 | 0.08 ± 0.01 |
Inulin renal CL, ml/min | 0.12 ± 0.03 | 0.19 ± 0.06 |
Corrected urinary recovery, % dosec | 95 ± 11 | 62 ± 12 |
TEA renal CL/GFR ratio | 5 | 1 |
↵a Noncompartmental parameters were calculated using mean concentrations in composite PK datasets, so variability and p values were not calculated.
↵b Urinary excretion was measured in a separate set of mice with four metabolic cages each containing three mice per group; mean ± S.E.M. for n = 4 metabolic cages; no statistically significant differences were observed between groups.
↵c Urinary recovery was corrected on the basis of the ratio of nominal-to-observed murine GFR (Bingham and Cummings, 1985). Nominal murine GFR is 0.28 ml/min (Davies and Morris, 1993), and observed GFR was measured by creatinine and inulin renal clearance.