Table 2.
Parameter estimates for the final population pharmacokinetic model for pantoprazole and pantoprazole-sulfone.
| Parameter | Estimate | RSE (%) | 2.5th %ile |
Bootstrap* median |
97.5th %ile |
|---|---|---|---|---|---|
| Structural model | |||||
| Ka# (1/h) | 7.49 | 32 | 4.66 | 7.97 | 17.4 |
| CL/F=θCL0+θ2c19*n10.5 (L/h, 70 kg) | |||||
| θCL0# | 1.45 | 12 | 1.15 | 1.47 | 1.75 |
| θ2C19CL# | 4.64 | 6 | 4.09 | 4.65 | 5.16 |
| Vc/F# (L, 70 kg) | 6.06 | 10 | 5.23 | 5.94 | 6.61 |
| Q/F# (L/h, 70 kg) | 1.86 | 29 | 1.20 | 1.97 | 3.09 |
| Vp/F# (L, 70 kg) | 1.61 | 20 | 1.17 | 1.68 | 2.25 |
| N# | 63.2 | 24 | 42.2 | 60.2 | 82.9 |
| MTT# (h) | 1.82 | 5 | 1.65 | 1.82 | 2.01 |
| Fm | 1 FIX | NA | NA | NA | NA |
| CLm/F (L/h, 70 kg) | 44.5 | 12 | 38.1 | 44.1 | 49.5 |
| Vcm/F (L, 70 kg) | 32.7 | 32 | 18.0 | 33.1 | 56.0 |
| Qm/F (L/h, 70 kg) | 274 | 8 | 237 | 271 | 328 |
| Vpm/F (L, 70 kg) | 310 | 7 | 275 | 309 | 358 |
| Inter-individual variability (% CV) | |||||
| CL/F | 26.9 | 21 | 21.9 | 26.4 | 32.1 |
| MTT | 28.5 | 21 | 22.3 | 28.3 | 34.7 |
| CLm/F | 60.7 | 59 | 50.5 | 59.8 | 69.8 |
| Vcm/F | 140.7 | 49 | 95.6 | 134 | 181 |
| Qm/F | 23.6 | 47 | 10.9 | 22.8 | 37.3 |
| Vpm/F | 34.4 | 37 | 23.2 | 33.8 | 48.4 |
| Residual error | |||||
| Proportional error, | 26.7 | 22 | 21.9 | 26.8 | 30.4 |
| pantoprazole (%) | |||||
| Proportional error, | 9.2 | 28 | 7.3 | 9.1 | 10.9 |
| pantoprazole-sulfone (%) | |||||
1000 bootstrap runs were performed for pantoprazole pharmacokinetic parameters (Ka, θCL0, θ2C19, Vc/F, Q/F, Vp/F, N, MTT); 500 bootstrap runs were performed for pantoprazole-sulfone pharmacokinetic parameters (CLm/F, Vcm/F, Qm/F, Vpm/F), inter-individual variability, and residual error parameters.
PK parameters, RSE and bootstrap results of pantoprazole were fixed to values of the final PK model for pantoprazole. CL/F, apparent clearance for pantoprazole; CLm/F, apparent clearance for pantoprazole-sulfone; CV, coefficient of variation; Fm, bioavailability for pantoprazole-sulfone; Ka, absorption rate constant; MTT, mean transit time; N, number of transit compartments; NA, not available; Q/F, apparent distributional clearance for pantoprazole; Qm/F, apparent distribution clearance for pantoprazole-sulfone; RSE, relative standard error; Vc/F, apparent volume for central compartment for pantoprazole; Vcm/F, apparent volume for central compartment for pantoprazole-sulfone; Vp/F, apparent volume for peripheral compartment for pantoprazole; Vpm/F, apparent volume for peripheral compartment for pantoprazole-sulfone.
The population mean estimate of CL/F (L/h) for an individual should be calculated as , where θCL0 = 1.45; θ2C19 = 4.64; n1 is the CYP2C19 number of functional alleles for the individual; TBW is the weight of the individual.