Table 1.

Single- and multiple-dose compartmental pharmacokinetic parameters of VER in plasmaa

Dose typeDose (mg/kg)Cmax (μg/ml)Cmin (μg/ml)AUC0–∞ (μg · h/ml)V1 (liters/kg)V2 (liters/kg)V3 (liters/kg)
Single0.100.515 ± 0.08<LLQ0.477 ± 0.0320.215 ± 0.0300.672 ± 0.1020.270 ± 0.035
0.251.486 ± 0.514<LLQ1.499 ± 0.0710.260 ± 0.0290.515 ± 0.0760.378 ± 0.000
0.501.704 ± 0.087<LLQ3.224 ± 0.2800.295 ± 0.0150.495 ± 0.0360.441 ± 0.037
13.209 ± 0.3660.050 ± 0.0259.153 ± 0.6660.320 ± 0.0340.374 ± 0.0340.350 ± 0.033
518.091 ± 2.5420.317 ± 0.04350.573 ± 3.8420.289 ± 0.0450.316 ± 0.0180.335 ± 0.032
1030.053 ± 3.0890.594 ± 0.05192.086 ± 2.8060.340 ± 0.0380.310 ± 0.0280.284 ± 0.020
2051.066 ± 2.9431.233 ± 0.167187.066 ± 7.9100.397 ± 0.0230.374 ± 0.0300.275 ± 0.020
P0.004ND0.0040.1160.0200.054
Multiple0.100.466 ± 0.027<LLQ0.712 ± 0.0490.219 ± 0.0130.439 ± 0.0270.295 ± 0.019
0.250.986 ± 0.074<LLQ2.014 ± 0.4460.262 ± 0.0200.588 ± 0.0370.382 ± 0.056
0.501.864 ± 0.0370.025 ± 0.0033.420 ± 0.1070.272 ± 0.0060.670 ± 0.0720.378 ± 0.009
12.982 ± 0.3980.074 ± 0.0047.973 ± 0.4330.358 ± 0.0450.468 ± 0.0080.605 ± 0.088
514.183 ± 2.2620.492 ± 0.08152.033 ± 5.1840.392 ± 0.0710.350 ± 0.0460.592 ± 0.041
1032.240 ± 10.8861.036 ± 0.139112.60 ± 14.8600.390 ± 0.1030.602 ± 0.0670.644 ± 0.116
2063.026 ± 2.9391.446 ± 0.118208.80 ± 24.2150.328 ± 0.0150.502 ± 0.0950.604 ± 0.131
P0.003ND0.0030.1380.0390.047
Vss (liters/kg)CL2 (liters/h/kg)CL3 (liters/h/kg)CLt (liters/h/kg)t1/2α(h)t1/2β(h)t1/2γ (h)
1.157 ± 0.0410.445 ± 0.0030.016 ± 0.0020.070 ± 0.0090.221 ± 0.0136.558 ± 0.93517.60 ± 1.025
1.153 ± 0.0460.440 ± 0.0020.021 ± 0.0010.103 ± 0.0050.237 ± 0.0114.498 ± 0.25416.150 ± 0.320
1.232 ± 0.0850.488 ± 0.0350.024 ± 0.0020.121 ± 0.0120.235 ± 0.0054.018 ± 0.15616.293 ± 0.075
1.043 ± 0.0550.528 ± 0.0300.020 ± 0.0020.097 ± 0.0060.209 ± 0.0124.071 ± 0.24216.017 ± 0.876
0.939 ± 0.0890.549 ± 0.0810.028 ± 0.0090.099 ± 0.0080.184 ± 0.0273.199 ± 0.42613.573 ± 2.411
0.934 ± 0.0430.598 ± 0.0670.030 ± 0.0010.109 ± 0.0030.179 ± 0.0132.914 ± 0.1659.764 ± 0.388
1.045 ± 0.170.471 ± 0.0850.018 ± 0.0020.109 ± 0.0050.287 ± 0.0694.176 ± 0.38513.620 ± 1.107
0.0520.3930.1040.0710.1600.0260.074
0.953 ± 0.0530.346 ± 0.0200.017 ± 0.0010.117 ± 0.0040.247 ± 0.0073.863 ± 0.18014.663 ± 0.203
1.231 ± 0.0480.504 ± 0.0290.021 ± 0.0020.127 ± 0.0210.214 ± 0.0074.376 ± 0.32316.013 ± 1.644
1.319 ± 0.0620.544 ± 0.0310.021 ± 0.0000.149 ± 0.0050.211 ± 0.0084.266 ± 0.35115.063 ± 0.222
1.430 ± 0.1380.486 ± 0.0350.030 ± 0.0040.126 ± 0.0090.258 ± 0.0053.861 ± 0.16518.343 ± 0.364
1.334 ± 0.0840.295 ± 0.0370.027 ± 0.0040.107 ± 0.0110.412 ± 0.1124.093 ± 0.70020.897 ± 1.161
1.636 ± 0.2240.766 ± 0.2810.029 ± 0.0090.118 ± 0.0180.285 ± 0.1514.920 ± 0.74422.437 ± 2.596
1.434 ± 0.2330.382 ± 0.1220.017 ± 0.0050.119 ± 0.0140.3870 ± 0.1264.802 ± 0.23530.230 ± 3.737
0.1160.1340.2230.3350.0490.3540.014
  • a All values represent the means ± standard errors of the means of three rabbits each.Cmin, concentration in plasma at the end of the recommended dosing interval (24 h); V1,V2, and V3, volume of distribution of the first, second, and third compartment, respectively; CL2 and CL3, distributional clearance; CLt, total plasma clearance;t1/2α, distributional half-life;t1/2β, apparent elimination half-life;t1/2γ, terminal elimination half-life. The LLQ was 0.020 μg/ml. P values were determined for the comparison among dosage groups by Kruskal-Wallis nonparametric ANOVA. ND, not determined.