Table 3.
Final covariate models for S- and R-warfarin
| S-Warfarin | R-Warfarin | |||||
|---|---|---|---|---|---|---|
| Objective function | 8899 | 9334 | ||||
| Parameter | Estimate | Standard error | 95% Confidence interval | Estimate | Standard error | 95% Confidence interval |
| CL (l h−1) | 0.144 | 0.00647 | (0.131, 0.157) | 0.125 | 0.00528 | (0.115, 0.135) |
| V (l) | 16.6 | 1.57 | (13.5, 19.7) | 10.9 | 1.16 | (8.63, 13.2) |
| Ka | 1.66 | Fixed | – | 1.66 | Fixed | – |
| θwgt | 0.321 | 0.145 | (0.037, 0.605) | 0.650 | 0.132 | (0.391, 0.909) |
| θage | −0.00816 | 0.00206 | (–0.0122, −0.00412) | −0.00657 | 0.00223 | (–0.0109, −0.00220) |
| θgender | ||||||
| Female | 1.00 | |||||
| Male | 1.12 | 0.0705 | (0.982, 1.26) | |||
| θCYP2C9 | ||||||
| *1/*1 (wild-type) | 1.00 | |||||
| *1/*2 | 0.855 | 0.0629 | (0.732, 0.978) | |||
| *2/*2 | 0.672 | 0.0568 | (0.561, 0.783) | |||
| *1/*3 | 0.454 | 0.0505 | (0.355, 0.553) | |||
| *2/*3 | 0.496 | 0.121 | (0.259, 0.733) | |||
| *3/*3 | 0.286 | 0.0324 | (0.222, 0.350) | |||
| Missing | 0.782 | 0.0899 | (0.606, 0.958) | |||
| θCYP2C19 | ||||||
| Homozygote | 1.00 | |||||
| Heterozygote | 0.761 | 0.0576 | (0.648, 0.874) | |||
| Mutant – homozygote | 0.494 | 0.191 | (0.120, 0.868) | |||
| Missing | 0.804 | 0.0523 | (0.701, 0.907) | |||
| θCYP3A4 | 1.00 | |||||
| Homozygote | 1.32 | 0.0978 | (1.13, 1.51) | |||
| Heterozygote | 1.06 | 0.172 | (0.723, 1.40) | |||
| Mutant – homozygote | 0.937 | 0.0845 | ().771, 1.10) | |||
| IIV CL* | 41.8% | (37.3%, 45.9%) | 43.0% | (38.6%, 47.0%) | ||
| IIV V* | 35.8% | (18.0%, 47.3%) | 38.3% | (20.2%, 50.3%) | ||
| Covariance (CL, V)† | 0.422 | 0.352 | ||||
| Proportional error* | 31.6% | (28.5%, 34.5%) | 31.9% | (29.2%, 34.5%) | ||
| Additive error (µg ml−1) | 1 | Fixed | 1 | Fixed | ||
*
Interindividual variability (IIV) and residual proportional error are expressed as an approximate coefficient of variation (square root of the variance).
†
Covariance is expressed as a correlation coefficient. Ka, absorption rate.