TABLE 3

Population pharmacokinetic parameters (mean ± S.D.) for the BZT analogs and cocaine after intravenous administration to male Sprague-Dawley rats

Cocaine dose, 5 mg/kg; BZT analog dose, 10 mg/kg.

Parameter
Cocaine
AHN 2-003
AHN 1-055
AHN 2-005
JHW 007
AUC (ng/h/l) 5932 ± 444 30,304 ± 8477 21,397 ± 6643 14,592 ± 3324 11,132 ± 1449
Cmax (ng/ml) 64,283 ± 2163 1239 ± 349 1477 ± 162 3389 ± 725 984 ± 95
Vss (l/kg) 0.9 ± 0.1 30.5 ± 11.9* 18.7 ± 2.3* 12.3 ± 3.2* 23.2 ± 3.2*
Clearance (l/h/kg) 3.1 ± 0.2 1.3 ± 0.5* 1.8 ± 0.5* 2.6 ± 0.6* 3.2 ± 0.4
t½-α (h) 0.01 ± 0.0003 0.17 ± 0.001* 0.09 ± 0.003* 0.21 ± 0.005* 0.31 ± 0.004*
t½-β (h) 0.49 ± 0.06 16.49 ± 0.11* 7.69 ± 1.76* 4.12 ± 0.33* 5.35 ± 0.48*
AUCBr/AUCplasma 2.1 2.0 4.8 6.6 5.6
Brain-t½-λz (h)
0.6
12.5
6.2
5.8
8.5

  • ↵* Significant difference (p < 0.05).