Table 2.
Comparison of PK parameter estimates obtained from sequential and simultaneous PKPD modeling approaches with SAEM
| Definition | Parameter | PK alone (PK estimation step of the two-stage approach) | Simultaneous PKPD | ||
|---|---|---|---|---|---|
| Population estimate | RSE (%) | Population estimate | RSE (%) | ||
| Total clearance | CL (l day−1) | 5500 | 6 | 5180 | 6 |
| Central volume | V2 (l) | 274 | 12 | 349 | 10 |
| Intercompartmental clearance | Q (l day−1) | 1140 | 8 | 1290 | 8 |
| Peripheral volume | V3 (l) | 1040 | 9 | 1130 | 9 |
| Absorption rate constant | ka (day−1) | 8.11 | 10 | 9.36 | 10 |
| Food effect on ka | Food on k a | −0.755a | 36 | −0.141c | 222 |
| Relative bioavailability | F1 | 1 FIX | – | 1 FIX | – |
| Food effect on F1 | Food on F1 | −0.244b | 45 | −0.476d | 14 |
| Absorption lag time | LagC (days) | 0.0211 | 10 | 0.0178 | 13 |
| IIV on CL | ω[CL] (%) | 46.6 | 9 | 46.9 | 9 |
| IIV on V2 | ω[V2] (%) | 60.6 | 16 | 55.5 | 15 |
| IIV on Q | ω[Q] (%) | 35.1 | 20 | 47.2 | 15 |
| IIV on V3 | ω[V3] (%) | 40.0 | 22 | 51.4 | 15 |
| IIV on ka | ω[ka] (%) | 64.1 | 11 | 69.9 | 11 |
| IIV on LagC | ω[LagC] (%) | 39.0 | 26 | 60.2 | 20 |
| Residual error | Additive error (%) | 45.4 | 2 | 44.6 | 2 |
a P value = 0.0049
b P value = 0.028
c P value = 0.65
d P value < 0.0001