TABLE 2

Pharmacokinetics of varenicline and total radioactivity in mice, rats, monkeys, and humans after oral administration of [14C]varenicline

Values represent mean ± S.D.




Mouse (3.0 mg/kg)

Rat (3.0 mg/kg)

Monkey (0.08 mg/kg)

Human (1.0 mg)a
Varenicline
    AUC(0-tlast) (ng · h/ml)b 963 2390 ± 610 210 ± 26 90.3 ± 6.8
    Cmax (ng/ml) 293 234 ± 55 19.3 ± 3.4 4.01 ± 0.71
    tmax (h) 1.0 1.8 ± 1.3 3.0 ± 1.0 4.3 ± 2.3
    t1/2 (h) 1.4 4.0 ± 0.9 24 ± 6 17 ± 3
    CL/F (ml/min/kg) 52 21 ± 5 6.3 ± 0.8 2.5 ± 0.2
Total Radioactivity:
    AUC(0-tlast) (ng Eq. · h/ml)b 1380 4340 ± 980 331 ± 34 114 ± 11
    Cmax (ng Eq./ml) 386 413 ± 82 29.0 ± 6.4 4.57 ± 0.47
    tmax (h) 1.0 2.4 ± 1.4 3.0 ± 1.0 2.8 ± 1.6
    t1/2 (h) 1.8 5.1 ± 0.6 30 ± 3 17 ± 2
Varenicline as percentage of total drug-related material
70
55
63
79
  • ng Eq., nanogram equivalents of varenicline-related material.

  • a Human dose was 1.0 mg, unadjusted for body weight.

  • b tlast values were 12 h (mouse), 24 h (rat, monkey), and 72 h (human).