Table 1.
Model parameters from the final EFV PK model in rhesus macaques and humans
| Parametera | Geometric mean | Median | CV% |
|---|---|---|---|
| Rhesus macaques | |||
| CL/F (L/hour) | 8.70 | 10.74 | 89.8 |
| V5/F (L) | 6.45 | 5.00 | 51.2 |
| Ka (1/hour) | 0.183 | 0.17 | 36.4 |
| V6/F (L) | 14.6 | 13.69 | 155.0 |
| Q/F (L/hour) | 4.66 | 5.9895 | 89.1 |
| TAU (1/hour) | 0.95 | 1.16 | 48.5 |
| Ma | 2.63 | 2.07 | 103.0 |
| Kplasma‐CSF (1/hour) | 1.71E‐06 | 1.91E‐06 | 59.5 |
| KCSF‐plasma (1/hour) | 0.18 | 0.18 | 27.3 |
| Kplasma‐brain (1/hour) | 2.42E‐03 | 2.34E‐03 | 31.1 |
| Kbrain‐plasma (1/hour) | 0.15 | 0.14 | 26.8 |
| KCSF‐brain (1/hour) | 2.56E‐03 | 0.002779 | 36.0 |
| Kbrain‐CSF (1/hour) | 5.58E‐06 | 4.6E‐06 | 68.2 |
| Vbrain/F (L) | 0.037 | 0.036 | 21.8 |
| VCSF/F (L) | 0.015 (fixed) | 0.015 (fixed) | — |
| Humansb | |||
| CL/F (L/hour) | 12.37 | 12.20 | 58.5 |
| V5/F (L) | 155.34 | 147.25 | 39.1 |
| Ka (1/hour) | 0.135 | 0.025 | 94.6 |
| V6/F (L) | 405.4 | 200.05 | 35.8 |
| Q/F (L/hour) | 6.31 | 28.33 | 142.0 |
| TAU (1/hour) | 1.00 | 1.95 | 27.8 |
| Kplasma‐CSF (1/hour) | 4.27E‐06 | 4.11E‐06 | 88.8 |
| KCSF‐plasma (1/hour) | 0.244 | 0.244 | 26.0 |
| Kplasma‐brain (1/hour) | 2.00E‐03 | 2.00E‐03 | 30.2 |
| Kbrain‐plasma (1/hour) | 0.175 | 0.175 | 31.2 |
| KCSF‐brain (1/hour) | 3.00E‐03 | 3.00E‐03 | 40.2 |
| Kbrain‐CSF (1/hour) | 2.41E‐06 | 2.41E‐06 | 70.5 |
| Vbrain/F (L) | 0.514 | 0.514 | 25.1 |
| VCSF/F (L) | 0.15 (Fixed) | 0.15 (Fixed) | — |
CL/F, total apparent clearance; CSF, cerebrospinal fluid; CV%, percentage of coefficient of variation; EFV, efavirenz; Ka, absorption rate constant; Kbrain‐CSF, rate constant for drug movement from brain tissue to CSF; Kbrain‐plasma, rate constant for drug movement from brain tissue to plasma; KCSF‐brain, rate constant for drug movement from CSF to brain tissue; KCSF‐plasma, rate constant for drug movement from CSF to plasma; Kplasma‐brain, rate constant for drug movement from plasma to brain tissue; Kplasma‐CSF, rate constant for drug movement from plasma to CSF; M, multiplicative term; PK, pharmacokinetic; Q/F, intercompartmental clearance; TAU, transit compartment clearance rate; Q/V, intercompartmental rate constants; V5/F, central compartment volume of distribution; V6/F, peripheral compartment volume of distribution; Vbrain/F, brain tissue volume of distribution; VCSF/F, CSF volume of distribution.
aM was not incorporated on the clearance term in the human EFV PK model. bThe human PK model was developed by a sequential estimation method where the plasma was initially estimated, followed by the central nervous system distributional parameters.