Table 2.
Parameters | Final model | Bootstrap n = 500 | ||
---|---|---|---|---|
Final estimate | RSE (%) | Median | 5th–95th percentile | |
Ka (h –1 ) | ||||
Ka = θ1× F ABCB1 | 0.0497 | 29.4 | 0.0509 | 0.0294–0.0870 |
F ABCB1 WT | 1 FIX | |||
F ABCB1 HET | 1.86 | 44.4 | 1.78 | 0.86–3.47 |
F ABCB1 MUT | 6.93 | 44.6 | 6.79 | 3.01–14.61 |
V 1 /F (l) | 0.513 | 25.2 | 0.508 | 0.295–0.921 |
V 2 /F (l) | 1 FIX | |||
V 3 /F (l) | 1 FIX | |||
CL OMZ‐M1 (l h –1 ) | ||||
CL OMZ‐M1 = θ2× F PNA × F CYP2C19 | ||||
θ2 | 0.658 | 21.4 | 0.676 | 0.474–0.943 |
F CYP2C19 EM/UM | 1 FIX | |||
F CYP2C19 IM | 0.449 | 25.6 | 0.463 | 0.299–0.726 |
F CYP2C19 PM | 0.125 | 44.5 | 0.111 | 0.030–0.149 |
F PNA = (PNA/38) θ3 | 0.472 | 29.2 | 0.482 | 0.185–0.795 |
CL OMZ‐M2 (l h –1 ) | 0.140 | 8.4 | 0.142 | 0.119–0.165 |
CL M1 /F (l h –1 ) | 0.846 | 18.4 | 0.863 | 0.614–1.167 |
CL M2 /F (l h –1 ) | 0.130 | 27.3 | 0.135 | 0.062–0.206 |
Interindividual variability (%) | ||||
Ka | 130.0 | 29.4 | 124.9 | 94.1–150.1 |
V 1 /F | 99.0 | 37.0 | 97.3 | 67.1–130.4 |
CL OMZ‐M1 | 52.6 | 25.3 | 50.8 | 39.9–59.0 |
CL OMZ‐M2 | 35.9 | 47.3 | 34.9 | 19.3–48.7 |
CL M1 /F | 55.9 | 30.8 | 54.1 | 38.1–66.6 |
CL M2 /F | 68.8 | 103.4 | 74.4 | 35.8–114.6 |
Residual additive (ng ml –1 ) | 55.6 | 50.2 | 50.4 | 31.6–71.0 |
Ka: absorption rate constant (h–1); V1/F: apparent volume of distribution of omeprazole; V2/F: apparent volume of distribution of 5‐hydroxy‐omeprazole; V3/F: apparent volume of distribution of omeprazole sulfone; CLOMZ‐M1: clearance of omeprazole converted to 5‐hydroxy‐omeprazole; CLOMZ‐M2: clearance of omeprazole converted to omeprazole sulfone; CLM1/F: apparent clearance of 5‐hydroxy‐omeprazole; CLM2/F: apparent clearance of omeprazole sulfone; FABCB1: scaling factors applied for ABCB1 homozygous wild‐type (WT); heterozygous (HET) and homozygous mutant (MUT); FCYP2C19: scaling factors applied for CYP2C19 extensive metabolizer (EM), ultrarapid metabolizer (UM); intermediate metabolizer (IM) and poor metabolizer (PM); PNA: postnatal age in days