Table 2.
Parameter estimates of the final population PK model
| Model parameter | Description | Estimate | RSE, %a | IIV (CV%) | Shrinkage, % |
|---|---|---|---|---|---|
| CL/F (l/h) | Apparent systemic clearance | 3.10 | 2.89 | 0.096 (31.7) | 31.9 |
| WT on CL/F | Weight exponent on CL/F | 0.494 | 0.0237 | – | – |
| V2/F (L) | Apparent volume of distribution of the central compartment | 11.7 | 2.47 | 0.154 (40.8) | 54.6 |
| WT on V2/F | Weight exponent on V2/F | 1.01 | 0.0247 | – | – |
| KA (h–1) | Absorption rate constant | 0.237 | 3.48 | 0.192 (45.9) | 47.9 |
| ALAG1 (h), healthy | Absorption lag time | 0.232 | 4.68 | 0.136 (38.2) | 54.5 |
| Chronic HBV infection on ALAG1 | Proportional shift for chronic HBV infection on ALAG1 | – 0.466 | 8.40 | – | – |
| Q3/F (l/h) | Apparent intercompartmental clearance between central and shallow peripheral compartments | 0.107 | 2.91 | 0.233 (51.2) | 54.1 |
| V3/F (L), healthy | Apparent volume of distribution of the shallow peripheral compartment | 33.2 | 1.98 | 0.448 (75.2) | 41.8 |
| Chronic HBV infection on V3/F | Proportional shift for chronic HBV infection on V3/F | – 0.337 | 2.56 | – | – |
| Q4/F (l/h) | Apparent intercompartmental clearance between central and deep peripheral compartments | 0.0428 | 2.69 | 1.140 (146.0) | 25.8 |
| V4/F (L) | Apparent volume of distribution of the deep peripheral compartment | 63.7 | 2.25 | 1.590 (198.0) | 15.4 |
| RV (CV%) | CCV residual error | 0.0449 (21.2) | 1.59 | – | 0.0986 |
CL/F (l/h) = 3.10 · (WT/73)^0.494; V2/F (L) = 11.7 · (WT/73)^1.01; ALAG1 (h) = 0.232 (healthy participants); ALAG1 (h) = 0.232 * (1–0.466) (participants with chronic HBV infection); V3/F (l/h) = 33.2 (healthy participants); V3/F (l/h) = 33.2 * (1–0.337) (participants with chronic HBV infection)
ALAG1 absorption lag time, CCV constant coefficient of variation, CL/F apparent clearance following extravascular administration, CV coefficient of variation, HBV hepatitis B virus, IIV interindividual variability, KA first-order absorption rate constant, Q3/F apparent intercompartmental clearance between central and shallow peripheral compartments following extravascular administration, Q4/F apparent intercompartmental clearance between central and deep peripheral compartments following extravascular administration, RSE relative standard error, RV residual variation, V2/F apparent central volume of distribution following extravascular administration, V3/F apparent volume of distribution of the shallow peripheral compartments following extravascular administration, V4/F apparent volume of distribution of the deep peripheral compartments following extravascular administration, WT body weight
aReported RSE% are for the log-transformed parameter values