Parameter | Population Mean | Intersubject Variabilitya | ||||
---|---|---|---|---|---|---|
Estimate | CVb | Estimate | CVc | |||
% | % | % | ||||
CHF3381 | ||||||
CLB (l/h) | 41.2 | 9 | 12g | 61 | ||
CLss (l/h) | 27.4 | 9 | 12g | 61 | ||
kCL (h-1) | 0.13 | 33 | ||||
ka (h-1) | 1.85 | 33 | 165 | 67 | ||
Lag time (h) | 0.2 | 12 | ||||
Q (l/h) | 1.7 | 12 | ||||
V (liters) | 131 | 4 | 12 | 64 | ||
Vp (liters) | 36 | 6 | ||||
CLR (percentage of CL)d | 4.3 | 9 | 12g | |||
σ (CV%)e | 46% | 5 | ||||
σ (CV%)f | 69% | 8 | ||||
CHF3567 | ||||||
CLM1 (l/h) | 3.4 | 3 | 16g | 57 | ||
VM1 (liters) | 67.2 | 5 | 16 | 79 | ||
CLRM1 (l/h) | 0.5 | 4 | 16g | 57 | ||
σ (CV%)e | 26% | 7 | ||||
σ (CV%)f | 34% | 27 | ||||
2-Aminoindane | ||||||
Vm (μg/h) | 67.2 | 7 | 16g | 50 | ||
km (μg/l) | 286 | 9 | ||||
VM2 (liters) | 3380 | 3 | 11 | 64 | ||
CLRM2 (l/h) | 0.002 | 4 | 16g | 50 | ||
σ (CV%)e | 27% | 8 | ||||
σ (CV%)f | 42% | 21 |
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CLB, baseline clearance; CLss, clearance at steady state; kCL, rate constant for the decrease of clearance from clearance baseline to clearance at steady state; ka, absorption rate constant; Q, intercompartmental clearance; V and Vp, apparent volumes of distribution in the central and the peripheral compartment for CHF3381; VM1 and VM2, apparent volume of distribution of M1 and M2; CLM1, clearance of M1; Vm, maximal rate of elimination of M2; km, concentration yielding 50% of Vm; CLR, renal clearance for CHF3381 expressed as percentage of total clearance (which changes over time, see text); CLRM1 and CLRM2, renal clearance for CHF3567 and 2-aminoindane, respectively.
↵ a Estimates of variability expressed as approximate coefficient of variation (CV%, √Μ · 100).
↵ b Standard error of the estimates (S.E.), defined as S.E./estimate, expressed as a percentage.
↵ c Standard error of the coefficient of variation, taken as √S.E.estimate/estimate, expressed as a percentage.
↵ d Expressed as percentage of total clearance (at any time).
↵ e Residual intrasubject variability of the plasma concentrations, expressed as coefficient of variation (CV%).
↵ f Residual intrasubject variability of the urine amounts, expressed as coefficient of variation (CV%).
↵ g The same random effect is associated with CLB, CLss and CLR, CLM1 and CLRM1, and Vm and CLRM2, respectively.