Table 3.
Population pharmacokinetic parameter estimates of models for TAC and MMF.
| Parameter | Independent model | Integrated model | ||
|---|---|---|---|---|
| Population mean value (%RSE) | IIV CV% (%RSE) | Population mean value (%RSE) | IIV CV% (%RSE) | |
| Tacrolimus | ||||
| CL/FTAC (L/h) | 17.8 (11%) | 50.9% (14%) | 13.8 (11%) | 26.4% (19%) |
| V2/F (L) | 108 (12%) | 44.4% (13%) | 93 (9%) | 30.8% (13%) |
| KaTAC (h−1) | 3.75 (60%) | 160% (36%) | 1.78 (43%) | 93% (18%) |
| k23 (h−1) | 0.326 (4%) | — | 0.313 (6%) | — |
| k32 (h−1) | 0.069 (5%) | — | 0.0719 (6%) | — |
| Lag time (h) | 0.627 (26%) | — | 0.59 (30%) | — |
| CYP3A5 on CL/F | 1.26 (7%) | — | 1.48 (16%) | — |
| σ prop TAC | 0.131 (13%) | — | 0.131 (12%) | — |
| Mycophenolic acid | ||||
| CL/FMPA (L/h) | 16.1 (7%) | 25.9% (35%) | 16.3 (7%) | 18.7% (32%) |
| V5/F (L) | 16.8 (12%) | 40.9% (28%) | 19.7 (11%) | 18.2% (27%) |
| KaMPA (h−1) | 2.06 (14%) | 69.7% (17%) | 2.29 (9%) | 56.6% (28%) |
| k56 (h−1) | 1.33 (6%) | — | 1.12 (10%) | — |
| k65 (h−1) | 0.109 (9%) | — | 0.131 (7%) | — |
| k70 (h−1) | 0.256 (10%) | — | 0.251 (13%) | — |
| V7/F (L) | 5.13 (7%) | — | 5.83 (7%) | — |
| fMPA | 0.85 fix | — | 0.85 fix | — |
| EHC (%) | 0.427 (10%) | 30.1% (22%) | 0.367 (15%) | 35.5% (18%) |
| k84 (h−1) | 263 (540%) | — | 18.4 (160%) | — |
| MTIME1 | 7.99 (0%) | — | 7.96 (1%) | — |
| MTIME2 | 1 fix | — | 1 fix | — |
| V9/F (L) | 23 fix | — | 23 fix | — |
| k90 (h−1) | 2.15 fix | — | 2.15 fix | — |
| σ prop MPA | 0.516 (9%) | — | 0.524 (7%) | — |
| σ add MPAG | 0.186 (44%) | — | 0.104 (31%) | — |
| σ prop MPAG | 0.172 (8%) | — | 0.237 (12%) | — |
| σ prop AcMPAG | 0.654 (31%) | — | 0.651 (22%) | — |
| Interaction | — | — | 0.0294 (154%) | — |
IIV, interindividual variability; CV, coefficient of variation; RSE, relative standard error; F, fraction of the dose absorbed; CL/F, apparent clearance; TAC, tacrolimus; V/F, apparent volume of distribution; Ka, first-order absorption rate constant; k23, k32, k56, and k65, intercompartment rate constants; MPA, mycophenolic acid; k70 and k90, eliminated rate constants; CYP3A5, CYP3A5 expressers (CYP3A5*1/*1 or CYP3A5*1/*3); fMPA, fraction of MPA which metabolized to MPAG; EHC, enterohepatic circulation; k84, gallbladder emptying rate constant; MTIME1, meal time; MTIME2, Gallbladder emptying duration; MPAG, MPA 7-O-glucuronide; AcMPAG, MPA acyl glucuronide; σprop, proportional residual error; σadd, additive residual error.