Table 2.
Parameter estimates of the base model, final model and bootstrap analysis
| Parameter | Base model (RSE %) [shrinkage] | Final model (RSE %) [shrinkage] | Starting dose model (RSE %) [shrinkage] |
|---|---|---|---|
| t lag (h) | 0.29 (17) | 0.38 (49) | 0.39 (12) |
| k a (l h –1 ) | 3.26 (19) | 3.58 (40) | 3.70 (13) |
| CL/F (l h –1 ) | 25.9 (3) | 23.0 (3) | 22.5 (3) |
| V 1 /F (l) | 655 (7) | 692 (8) | 685 (5) |
| Q/F (l h –1 ) | 10.5 (7) | 11.6 (10) | 10.6 (6) |
| V 2 /F (l) | 6320 (14) | 5340 (22) | 6590 (14) |
| Covariate effect on CL | |||
| CYP3A5*1 | ‐ | 1.63 (15) | 1.62 (14) |
| CYP3A4*22 | ‐ | 0.80 (32) | 0.81 (36) |
| Haematocrit (l l –1 ) | ‐ | −0.76 (11) | ‐ |
| Creatinine (μmol l –1 ) | ‐ | −0.14 (26) | ‐ |
| Albumin (g l –1 ) | ‐ | 0.43 (30) | ‐ |
| Age (years) | ‐ | −0.43 (19) | −0.50 (15) |
| BSA (m 2 ) | ‐ | 0.88 (24) | 0.72 (29) |
| Covariate effect on V 1 | |||
| Lean bodyweight (kg) | ‐ | 1.52 (20) | ‐ |
| IIV (%) | |||
| CL/F | 46.3 (5) 10 | 38.6 (6) 8 | 39.4 (6) 10 |
| V 1 /F | 50.2 (11) 19 | 49.2 (7) 25 | 54.0 (11) 19 |
| V 2 /F | 52.3 (14) 38 | 53.0 (16) 39 | 53.7 (13) 40 |
| Q/F | 79.6 (12) 29 | 78.7 (11) 28 | 79.6 (11) 29 |
| IOV (%) | |||
| CL/F | 15.1 (9) | 13.6 (10) | 14.6 (9) |
| Residual variability | |||
| Proportional (%) | |||
| Immunoassay | 16.6 (6) 26 | 17.7 (7) 22 | 16.9 (6) 25 |
| LC–MS/MS | 24.7 (5) 12 | 24.5 (5) 12 | 24.4 (5) 12 |
| Additive Immunoassay (μg l –1 ) | 1.02 (9) 26 | 0.88 (13) 22 | 1.02 (10) 25 |
CL, clearance; CYP, cytochrome P450; F, bioavailability of oral tacrolimus; IIV, interindividual variability; IOV, interoccasion variability; Ka, absorption rate constant; LC–MS/MS, liquid chromatography–tandem mass spectrometry; OFV, objective function value; Q, intercompartmental clearance of tacrolimus; RSE, residual standard error; tlag, lag time; V1, central compartment for tacrolimus; V2, peripheral compartment for tacrolimus