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. 2018 Mar 9;84(5):997–1005. doi: 10.1111/bcp.13526

Table 2.

Population pharmacokinetic parameters of omeprazole and its metabolites and bootstrap validation

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