TABLE 3.
Parameter estimates for the basic and covariate model of tenofovir and emtricitabine concentrations collected in 34 patients of the ANRS 134-COPHAR 3 triala
| Parameter (unit) | Base model |
Covariate model |
||
|---|---|---|---|---|
| Estimate | RSE (%) | Estimate | RSE (%) | |
| Population values | ||||
| Tlag TFV (h) | 0.348 | 32 | 0.337 | 40 |
| Ka TFV (h) | 2.45 | 32 | 2.25 | 33 |
| CL/FTFV (L/h) | 114 | 8 | 228 | 27 |
| βCL/FTFV,age | −0.017 | 38 | ||
| Vc/FTFV (L) | 398 | 12 | 381 | 14 |
| Q/FTFV (L/h) | 811 | 8 | 781 | 11 |
| Vp/FTFV (L) | 1420 | 11 | 4570 | 46 |
| βVp/FTFV,age | −0.029 | 40 | ||
| Vmax TFV-DP (μmol/L/h) | 0.006 | 10 | 0.006 | 10 |
| Km TFV-DP (μmol/L) | 0.102 | Fixed | 0.102 | Fixed |
| kem TFV-DP (h) | 0.006 | Fixed | 0.006 | Fixed |
| Tlag FTC (h) | 0.421 | 26 | 0.377 | 30 |
| Ka FTC (h) | 1.37 | 21 | 1.45 | 23 |
| CL/FFTC (L/h) | 18.1 | 5 | 28.0 | 16 |
| βCL/FFTC,age | −0.010 | 35 | ||
| Vc/FFTC (L) | 75.9 | 5 | 75.2 | 5 |
| Q/FFTC (L/h) | 4.48 | 21 | 46 | 16 |
| Vp/FFTC (L) | 121 | 21 | 120 | 18 |
| Vmax FTC-TP (μmol/L/h) | 1.42 | 17 | 1.49 | 17 |
| Km FTC-TP (μmol/L) | 0.946 | Fixed | 0.946 | Fixed |
| kem FTC-TP (h) | 0.0176 | Fixed | 0.0176 | Fixed |
| Interindividual coefficient of variation (%) | ||||
| ωTlag TFV | 127 | 22 | 150 | 41 |
| ωKa TFV | 116 | 20 | 113 | 22 |
| ωCL/FTFV | 38 | 13 | 35 | 13 |
| ωVp/FTFV | 57 | 15 | 50 | 17 |
| ωVmax TFV-DP | 29 | 31 | 26 | 32 |
| ρCL/FTFV, Vp/FTFV | 0.78b | 11 | 0.73b | 14 |
| ωTlag FTC | 116 | 18 | 122 | 20 |
| ωKa FTC | 83 | 19 | 90 | 19 |
| ωCL/FFTC | 28 | 15 | 24 | 14 |
| ωQ/FFTC | 82 | 27 | 63 | 21 |
| ωVmax FTC-TP | 44 | 28 | 43 | 44 |
| ρCL/FFTC, Q/FFTC | 0.76b | 15 | 0.69b | 20 |
| Residual coefficient of variation (%) | ||||
| σTFV | 16 | 7 | 15 | NE |
| σTFV-DP | 19 | 24 | 20 | 29 |
| σFTC | 20 | 9 | 20 | 8 |
| σFTC-TP | 30 | 31 | 28 | 26 |
RSE, relative standard error; TFV, tenofovir (plasma concentrations); TFV-DP, tenofovir diphosphate (intracellular concentrations); FTC, emtricitabine (plasma concentrations); FTC-TP, emtricitabine triphosphate (intracellular concentrations); Tlag, time delay in absorption; Ka, absorption rate constant; CL/F, apparent elimination clearance; Vc/F, apparent central compartment of distribution; Q/F, apparent intercompartmental clearance; Vp/F, apparent peripheral compartment of distribution; Vmax, maximal uptake rate constant; Km, Michaelis-Menten constant; kem, elimination rate constant from the cell; βPK parameter, covariate, additive effect size of covariate on log PK parameter with a βCL/FTFV,age of −0.017 indicating CL/FTFV decreases of 15 and 39% in patients 10 and 30 years older than the median age (38.5 years), a βVp/FTFV,age of −0.029 indicating Vp/FTFV decreases of 25 and 58%, and a βCL/FFTC,age of −0.010 indicating CL/FFTC decreases of 10 and 26%; NE: not estimated due to numerical issue.
Correlation estimates are not in percent.