TABLE 4

Population estimates of the pharmacodynamic parameters of CHF3381

Parameter
Population Mean
Intersubject Variabilityb
Estimate
S.E.c
 Estimate
S.E.d
% % %
DHPG concentrationa
    kin (ng h-1) 2540 19 20 76
    kout (h-1) 2.53 17 18 79
    EC50 (μg/l) 1670 8
    αe 1
    AC50 (mg) 241 38 109 81
    β 0.85 4
    σ (CV %)f 14% 13
Heart rate
    α/E0 (bpm/μg l-1) 0.0055 18 66 70
    E0 (bpm) 59.9 2 8 45
    σ (CV %)f
8%
12

  • kin, zero order production rate of DHPG; kout, elimination rate of DHPG; α, fractional decrease in kin; EC50, concentrations of CHF3381 at half of α; β, fractional decrease in baseline due to amount of CHF3381 absorbed, and AC50 total amount at half of β (see text).

  • ↵ a DHPG plasma concentrations were used as a marker of MAO-A enzyme activity.

  • ↵ b Estimates of variability expressed as approximate coefficient of variation (CV%, √Ω · 100).

  • ↵ c Standard error of the estimates, defined as S.E.estimate/estimate, expressed as a percentage.

  • ↵ d Standard error of the coefficient of variation, taken as √S.E.estimate/estimate, expressed as a percentage.

  • ↵ e Fixed.

  • ↵ f Residual intrasubject variability of the dynamic measure, expressed as coefficient of variation (CV %).