Table 2.
Parameter estimates of the final lopinavir pharmacokinetic model in COVID-19 patients
| PK parameters | Unit | Estimation | RSE (%) | Shr (%) | Bootstrap | ||
|---|---|---|---|---|---|---|---|
| 0.025 | median | 0.975 | |||||
| KA (fixed)a | h−1 | 0.572 | – | ||||
| CL0/F | L/h | 4.88 | 22.1 | 17.4 | 0.15 | 3.93 | 18.7 |
| V/F | L | 94.8 | 29.9 | 11.2 | 35.5 | 106 | 1325 |
| IC50 (fixed)a | mg/L | 0.057 | – | ||||
| Imax (fixed)a | 0.929 | – | |||||
| Inter-individual variability (ω) | |||||||
| CL | 2.881 | 35.4 | 13.4 | 0.30 | 2.57 | 40.4 | |
| V | 0.801 | 19.9 | 20.0 | 0.003 | 0.98 | 2.97 | |
| Residual unexplained variability (σ) | |||||||
| Proportional | 0.186 | 25.4 | 0.09 | 0.178 | 0.294 | ||
| Additive (fixed) | mg/L | 0.071 | – | ||||
KA, first-order absorption rate constant; CL0/F, apparent clearance without ritonavir; V/F, apparent volume of distribution; IC50, ritonavir concentration associated with half the maximal inhibition of the lopinavir CL/F; CresRTV, trough ritonavir concentration (mg/L); Imax, maximum inhibitory effect of ritonavir on the lopinavir CL/F; RSE, relative standard error; Shr, shrinkage
aRef (10)
CL/F = CL0/F × [1 – (Imax × CresRTV)/(IC50 + CresRTV)]