TABLE 1.
Cohort and dose (mg/kg) | Cmax (μg/ml) | Cmin (μg/ml) | AUC0-24 (μg·h/ml) | V1 (liter/kg) | V2 (liter/kg) | V3 (liter/kg) | Vss (liters/kg) | CL2 (liter/h/kg) | CL3 (liter/h/kg) | CLt (liter/h/kg) | t1/2α (h) | t1/2β (h) | t1/2γ (h) |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
LNYS | |||||||||||||
2 | 17.00 ± 0.62 | ND | 17.08 ± 0.48 | 0.093 ± 0.003 | 0.063 ± 0.001 | NA | 0.155 ± 0.003 | 0.1260 ± 0.019 | NA | 0.1173 ± 0.003 | 0.17 ± 0.01 | 1.10 ± 0.00 | NA |
4 | 39.27 ± 0.79 | ND | 42.74 ± 5.25 | 0.075 ± 0.001 | 0.063 ± 0.004 | NA | 0.138 ± 0.003 | 0.1233 ± 0.010 | NA | 0.0928 ± 0.012 | 0.16 ± 0.00 | 1.26 ± 0.09 | NA |
6 | 56.01 ± 0.42 | ND | 77.12 ± 9.65 | 0.085 ± 0.000 | 0.059 ± 0.002 | NA | 0.145 ± 0.002 | 0.1365 ± 0.006 | NA | 0.0805 ± 0.010 | 0.16 ± 0.01 | 1.44 ± 0.18 | NA |
DAMB, 1 | 3.36 ± 0.42 | 0.25 ± 0.03 | 12.23 ± 0.95 | 0.241 ± 0.040 | 0.631 ± 0.002 | 0.3306 ± 0.027 | 1.200 ± 0.043 | 0.2016 ± 0.015 | 0.4906 ± 0.040 | 0.0552 ± 0.007 | 0.16 ± 0.01 | 1.15 ± 0.07 | 16.82 ± 1.60 |
All values represent the means ± SEM of results for three rabbits each. Cmin, concentration in plasma at the end of the recommended dosing interval (24 h); V1, V2, V3, volume of distribution of the first, second, and third compartment, respectively; CL2, CL3, distribution clearances; t1/2α, distributional half-life; t1/2β, apparent elimination half-life; t1/2γ, terminal elimination half-life; ND, not detectable; NA, not applicable.
P values (based on Kruskal-Wallis nonparametric ANOVA): for Cmax, <0.0001; for AUC0-24, <0.0001; for V1, <0.0001; for V2, <0.0382; for Vss, 0.0028; for CL2, 0.0599; for CLt, 0.0137; for t1/2α, 0.9006; for t1/2β, 0.2775.