Parameter | Unit | Population mean value | RSE (%)* | Description |
---|---|---|---|---|
Fixed effects | ||||
TVCL_week3/F | l/hour | 3.52 | 0.98 | Typical subject's apparent oral clearance (Week 3) with median body weight of 62 kg |
Diff_CL_week27/F | % difference vs Week 3 | –6.55 | 13.0 | Difference in typical subject's apparent oral clearance (Week 27, expressed as percentage change to Week 3 value) |
V2/F | L | 51.6 | 3.64 | Apparent central volume of distribution |
V3/F | L | 204 | 7.99 | Apparent peripheral volume of distribution |
Q3/F | l/hour | 17.5 | 4.62 | Apparent inter-compartmental clearance |
ka | 1/hour | 2.18 | 8.26 | Absorption rate constant |
ALAG | hour | 0.372 | 2.54 | Lag-time |
F | – | 1 | – | Relative bioavailability |
Fixed covariate effects | ||||
CL_BW | %/kg | 0.672 | 14.5 | Influence of body weight on clearance (percentage of change in clearance per kilogram body weight; difference to median body weight) |
Random effects: inter-individual variability (IIV) and inter-occasion variability (IOV) | ||||
IIV_CL/F† | CV% | 55.4 | 7.89 | Inter-individual variability of clearance |
IIV_F† | CV% | 47.6 | 9.56 | Inter-individual variability of relative bioavailability |
ρ_CL/F,F (IIV) | – | 0.91 | 20.1 | Correlation coefficient of the variability of CL/F*F |
IOV_F† | CV% | 19.5 | 3.11 | Inter-occasion variability of relative bioavailability |
Random effects: residual error | ||||
Proportional error† | CV% | 9.61 | 1.88 | Proportional residual error |
Additive error | μg/l | 0.95 | 26.0 | Additive residual error |
CO2 = (1 CL_BW* (BW–62)).
CL = TVCL_week3* (1+TVCL_visit5*OCA)*EXP(ETA(1))*CO2.
*Relative standard error (RSE), expressed as percentage of estimate.
†Coefficient of variation (CV%), calculated as square root of (EXPOMEGA–1) x 100.
The calculation of the RSE of the CV% is based on a first-order Taylor expansion of the CV%; the CV% is assumed to be normally distributed.
F, bioavailability; CL, clearance.