TABLE 2.
Parameter estimates for final population PK model for doravirinea
| Parameter | Final estimate | % RSE | % CV | Lower 5% | Upper 95% | η shrinkage |
|---|---|---|---|---|---|---|
| Fixed effects | ||||||
| CL/F (liters/h) | 6.34 | 1.37 | 6.17 | 6.51 | ||
| V/F (liters) | 162 | 3.17 | 152 | 172 | ||
| Ka (1/h) | 1.40 | 4.57 | 1.28 | 1.53 | ||
| F1 < 30 mg | 1.20 | 5.87 | 1.06 | 1.34 | ||
| F1 30–120 mg (reference) | 1.00 | |||||
| F1 > 120 mg | 0.895 | 9.32 | 0.732 | 1.06 | ||
| Age on CL/F | −0.00508 | 16.6 | −0.00673 | −0.00343 | ||
| Healthy vs HIV-1 status on V/F | −0.220 | 12.3 | −0.273 | −0.167 | ||
| Wt on V/F | 0.00788 | 15.4 | 0.00551 | 0.0102 | ||
| Interindividual variability | ||||||
| CL/F | 0.117 | 7.93 | 35.2 | 0.0986 | 0.135 | 11.4 |
| V/F | 0.101 | 8.26 | 32.6 | 0.0848 | 0.118 | 38.7 |
| Residual variability (SD) | ||||||
| Phase 1 for ≤0.5 h | 0.224 | 3.77 | 22.4 | 0.207 | 0.241 | |
| Phase 1 for >0.5 h | 1.25 | 6.89 | 125 | 1.08 | 1.42 | 7.37 |
| Phase 2b/3 | 0.521 | 4.01 | 52.1 | 0.48 | 0.562 |
Clearance and the volume of distribution were calculated as follows: CLi = CLTV [1 + θ(agei − 34)] and Vi = VTV [1 + θweight(weighti − 75)]·(1 + θhealthy·flag), where CLi is the clearance for individual i, CLTV is the typical value for clearance, agei is the age of individual i, Vi is the volume of distribution for individual i, VTV is the typical value of the volume of distribution, θ is the estimated effect of age, θweight is the estimated effect of weight, θhealthy is the estimated effect of health status, weighti is the weight of individual i, and flag is equal to 1 for healthy volunteers and 0 for HIV-infected individuals (the most common population). CL/F, apparent clearance; CV, coefficient of variation; F1, oral bioavailability; Ka, absorption rate; RSE, relative standard error; V/F, apparent volume of distribution.