Table 4. Population pharmacokinetic model selected by the automated stepwise covariate model (SCM) building algorithm in Monolix.
Renal function, estimated as eGFR by the 2021 CKD-EPI equation using both serum cystatin C and serum creatinine, and age were selected as covariates of the elimination rate, k.
| Final Model | 2-compartment, linear elimination eGFRcys, Scr & Age as covariates on k |
|---|---|
| Model comparison | |
| AIC | 2427.31 |
| ΔAIC vs. structural model+ | −54.15 |
| Fixed-effect parameters | |
| V_pop (L) | 17.1 |
| k_pop (h−1) | 0.22 (6.47%) |
| k12_pop (h−1) | 0.46 (20.4%) |
| k21_pop (h−1) | 0.18 (11.8%) |
| βeGFR on k|| | 0.45 (16.5%) |
| βAge on k|| | −0.52 (39.8%) |
| Random-effect parameters | |
| Standard deviation of inter-individual variability (IIV) | |
| ωV | 0.3 (22.8%) |
| ωk | 0.43 (13.7%) |
| ωk12 | 0.15 (123%) |
| ωk21 | 0.62 (31.6%) |
| Residual variability (RV) | |
| b | 0.36 (8.06%) |
Comparison is to the 2-compartment structural model described in Table 2.
k = k_pop × (eGFR/30) βeGFR × (Age/60) βAge.
CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; eGFR: estimated glomerular filtration rate using equations that leverage self-identified black race (race), serum creatinine (cr), and/or serum cystatin C (cys); AIC: Akaike information criteria; V_pop: fixed population parameter for volume of distribution; k_pop: fit population parameter for the elimination rate; k12_pop and k21_pop: fit population parameter for the rate into/out of second compartment; ωV, ωk, ωk12, ωk21: standard deviation of random effects for population parameters; b: estimated value from proportional error model.