TABLE 7.
Final population pharmacokinetic estimates from bootstrap results for rifampin and desacetyl rifampin plasma concentrations and dried blood spot concentrations for nine healthy volunteersa
| Parameter | Value |
P value | |||
|---|---|---|---|---|---|
| Plasma parameter |
Relative difference in DBS parameter |
||||
| Estimate | 95% CI | Estimate | 95% CI | ||
| Objective function value | −183.8335 | −284.4266 to −118.4457 | |||
| Structural model parameters | |||||
| ka, RIF (/h) | 3.69 | 1.85 to 15.14 | 1.36 | 0.8 to 1.97 | 0.30 |
| MTTRIF (h) | 0.84 | 0.66 to 1.14 | 0.94 | 0.87 to 1.02 | 0.11 |
| NNRIF | 19.2 | 90.0 to 39.0 | 1.23 | 0.92 to 1.59 | 0.19 |
| CL/FRIF (liters/h/70 kg) | 7.65 | 5.88 to 9.80 | 1.18 | 1.06 to 1.33 | <0.01 |
| VC/FRIF (liters/70 kg) | 40.6 | 32.8 to 50.5 | 1.15 | 1.03 to 1.31 | <0.01 |
| CL/F*D-RIF (liters/h/70 kg) | 60.7 | 42 to 72.6 | 1.02 | 0.92 to 1.54 | 0.73 |
| VC/F*D-RIF (liters/70 kg) | 19.8 | 6.6 to 34.0 | 1.3 | 0.47 to 2.53 | 0.40 |
| Q/F*D-RIF (liters/h/70 kg) | 37.7 | 29.1 to 65.7 | 1.09 | 0.60 to 1.87 | 0.71 |
| VP/F*D-RIF (liters/70 kg) | 157 | 98 to 383 | 1.05 | 0.25 to 1.67 | 0.84 |
| Variable model parameters (shrinkage %) | |||||
| IIV in ka, RIF (%) | 118 | 50 to 225 | 1.11 | 0.82 to 1.39 | 0.41 |
| IIV in MTTRIF (%) | 32 | 12 to 42 | 1.02 | 0.93 to 1.09 | 0.58 |
| IIV in CL/FRIF (%) | 19 | 2 to 27 | 0.58 | 0.22 to 1.00 | 0.06 |
| IIV in CL/F*D-RIF (%) | 13 | 4 to 38 | 1.45 | 0.57 to 2.92 | 0.19 |
| IIV in VC/F*D-RIF (%) | 84 | 17 to 167 | 0.58 | 0.2 to 1.19 | 0.13 |
| RV for rifampin (%) | 25 | 19 to 31 | 1.12 | 0.85 to 1.36 | 0.56 |
| RV for desacetyl rifampin (%) | 31 | 19 to 39 | 0.91 | 0.71 to 1.09 | 0.29 |
ka, RIF, absorption rate constant for RIF; MTTRIF, mean transit time for RIF; NNRIF, number of transit compartments for RIF; CL/FRIF, clearance relative to bioavailability for RIF; VC/FRIF, central volume of distribution relative to bioavailability for RIF; CL/F*D-RIF, clearance relative to bioavailability and metabolic conversion for Des-RIF; VC/F*D-RIF, central volume of distribution relative to bioavailability and metabolic conversion for Des-RIF; Q/F*D-RIF, intercompartmental clearance and metabolic conversion for Des-RIF; VP/F*D-RIF, peripheral volume of distribution relative to bioavailability and metabolic conversion for Des-RIF; IIV, interindividual variability; RV, residual variability. IIV and RV are presented as .