Table 3:
Final parameter estimates for efavirenz
| Parameter | Typical Value (95% CIa) | Variability, %CV (95% CI) |
|---|---|---|
| CLintric (L/h) CYP2B6 normal | 2690 (2300 – 3030) | 53.8 (48.9 – 59.2)* |
| CLintric (L/h) CYP2B6 intermediate | 1940 (1790 – 2100) | |
| CLintric (L/h) CYP2B6 slow | 545 (487 – 624) | |
| Vcd (L) | 135 (109 – 165) | |
| Vpd (L) | 512 (487 – 623) | |
| Q/Fc (L/h) | 26.9 (19.8 – 36.5) | |
| Ka (1/h) | 1.75 FIXED | 180 (114.9– 227)# |
| MTT (h) | 1.78 (1.20 – 2.39) | 131 (103– 166)# |
| NN | 48.4 (11.3 – 64.7) | |
| QHc (L/h) | 90 FIXED | |
| Fu (%) | 0.5 FIXED | |
| Prehepatic relative Bioavailability | 1 FIXED | 23.2 (20.7 – 26.1)# |
| Proportional Error (%) | 6.91 (4.72 – 9.45) | |
| Additive Error (mg/L) | 0.353 (0.303 – 0.408) | |
| Pregnancy Effect on CL (%) | +15.9 (9.75 – 21.9) | |
| INH effect on CL/F (L/h) in CYP2B6 Fast metabolizers (%) | −6.87 (−12.1 – −1.13) | |
| INH effect on CL/F (L/h) in CYP2B6 Inter and slow metabolizers (%) | −13.4 (−17.3 – −9.06) |
Abbreviations: CLint clearance intrinsic; Vc apparent central volume of distribution for INH; VP apparent peripheral volume of distribution for INH; Q/F apparent intercompartmental clearance for INH; Ka first-order rate constant of INH absorption; MTT absorption mean transit time; NN Number of absorption transit compartment; QH blood liver flow; fu unbound fraction of efavirenz in plasma.
95% confidence intervals (CIs) were obtained with the SIR procedure
Variability was modelled with log-normal distribution and is presented as an approximate percentage CV.
Clearance parameters are allometrically scaled based on fat-free mass (typical value reported for 39 kg which was the median fat-free mass weight of the study population)
Volume pf distribution parameters are scaled based on weight (typical value reported for 67 kg which was the median weight of the study population).
Between subject variability.
Between occasion variability