Parameter | Unit | Population mean value | RSE (%)* | Description |
---|---|---|---|---|
Fixed effects | ||||
TVCL/F | l/hour | 25.3 | 1.24 | Typical subject's apparent oral clearance with median age of 24 years and median body weight of 62 kg |
V2/F† | l | 23.9 | 13.6 | Apparent central volume of distribution |
V3/F | l | 1,330 | 3.62 | Apparent deep peripheral volume of distribution |
V4/F† | l | 23.9 | — | Apparent peripheral volume of distribution |
Q3/F | l/hour | 52.9 | 7.01 | Apparent inter-compartmental clearance to deep compartment |
Q4/F | l/hour | 8.49 | 34.3 | Apparent inter-compartmental clearance |
ka | 1/hour | 0.295 | 6.98 | Absorption rate constant |
F_week3 | — | 1 | — | Relative bioavailability (Week 3) |
Diff_F_week27 | % difference from Week 3 | 8.15 | 11.0 | Difference in relative bioavailability (Week 27) (percentage change to Week 3 value) |
ALAG | hour | 0.353 | 2.78 | Lag-time |
Fixed covariate effects | ||||
CL_AGE | %/LN(year) | 20.8 | 29.1 | Influence of age on clearance [percentage of change in clearance per year of age (natural logarithm of the value); difference to median age] |
CL_BW | %/kg | 0.591 | 20.1 | 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) | ||||
IIV_CL‡ | CV% | 33.4 | 2.65 | Inter-individual variability of clearance |
Random effects: residual error | ||||
Proportional error‡ | CV% | 24.4 | 1.38 | Proportional residual error |
F = F_week3 * (1 + F_week27 *OCA); (week3: OCA = 0, other visits: OCA = 1).
CL = TVCL*EXP(ETA_CL)*CO2*CO1;
(CO1 = (1 + CL_AGE * (LOG(AGE)–LOG(24)), CO2 = (1 + CL_BW*(BW–62))).
*Relative standard error (RSE), expressed as percentage of estimate.
†For the model it was assumed that V2F = V4F.
‡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.