TABLE 1

Amantadine PK parameters by species

Mouse, Sexes Combined
10 mg/kg30 mg/kg60 mg/kgMeana
NCA parameter
Cmax (ng/ml)126837338826
Cmax/dose (ng/ml)/(mg/kg)127124147
 Tmax (h)0.250.50.25
 AUCinf (ng/h per milliliter)1781552213,877
 AUCinf/dose (ng/h per milliliter)/(mg/kg)178184231
t1/2 (h)1.11.01.5
Modeled parameters (using C(T) = D/V × exp(–K10 × T))
 V (ml/kg)6378645954366091
 K10 (1/h)0.84240.78110.80750.810
Rat, Sexes Combined
15 mg/kg45 mg/kg90 mg/kgMeanb
NCA parameter
Cmax (ng/ml)2769698224,899
Cmax/dose (ng/ml)/(mg/kg)185155277
 Tmax (h)0.250.250.25
 AUCinf (ng/h per milliliter)419914,11452,563
 AUCinf/dose (ng/h per milliliter)/(mg/kg)280314578
t1/2 (h)1.181.951.91
Modeled parameters (using C(T) = A × exp(–alpha × T) + B × exp(–beta × T))
 V1 (ml/kg)3816386215183839
 K10 (1/h)0.870.771.090.82
 K12 (1/h)0.611.633.491.12
 K21 (1/h)1.141.682.311.41
Cynomolgus Macaque, Sexes Combined
1 mg/kg3 mg/kg10 mg/kg30 mg/kgMeanc
NCA parameter
Cmax (ng/ml)16153915994633
Cmax/dose (ng/ml)/(mg/kg)161180160154
Tmax (h)4.03.53.755.75
 AUCinf (ng/h per milliliter)2287571021,74665,372
 AUCinf/dose (ng/h per milliliter)/(mg/kg)2287190321752179
t1/2 (h)11.56.496.956.27
Modeled parameters (using C(T) =K × (D/V) × T × exp(–K × T))
 V_F (ml/kg)24662171232426632406
 K (1/h)0.30.320.260.220.274
 Tlag (h)d0.390.450.410.520.440
  • A and B, coefficients; alpha, alpha phase elimination rate constant; beta, beta phase elimination rate constant; D, dose administered; K and K01 and K10 and K21, rate constant; NCA, noncompartmental analysis; Tlag, time lag; Tmax, time to Cmax; t1/2, half-life; V, volume; V_F, apparent volume; V1, volume of central compartment.

  • a Mean of 10, 30, and 60 mg/kg doses used to simulate the 40 mg/kg PK profile.

  • b Mean of 15 and 45 mg/kg doses used to simulate 10, 20, and 40 mg/kg PK profile.

  • c Mean of 1, 3, 10, and 30 mg/kg doses used to simulate PK profiles.

  • d Tlag max = 1.73 h.