TABLE 4.
Parameter values estimated by the final pharmacokinetic model for pyrazinamide
| Parameter | Estimated population value (95% CI) | % variability (95% CI), shrinkagea |
|
|---|---|---|---|
| Interoccasional | Interindividual | ||
| Bioavailability (F) | 1 (fixed) | 13.1 (10.2–16), 31 | |
| Mean transit time (h) | 0.74 (0.65–0.84) | 54.5 (45.1–63.9), 19 | |
| No. of absorption transit compartments | 2.06 (1.59–2.53) | ||
| Absorption rate constant (h−1) | 50.0 (fixed)c | ||
| Vol of distribution (liters)b | 41.9 (40.4–43.4) | ||
| CL/F (liters/h)b | 4.17 (3.90–4.44) | 29.6 (24.7–34.5), 8 | |
| Additive error (mg/liter) | 1.95 (1.77–2.13) | ||
| Proportional error (%) | 10.7 (9.60–11.80) | ||
a
Interindividual and -occasional variabilities were assumed to be lognormally distributed and are reported here as approximate % CV. For interoccasional variability terms, the shrinkage is reported only for the occasion with intensive sampling (not the predose).
b
All clearance and volume parameters were allometrically scaled using individual values for fat-free mass (FFM), so the typical values reported here refer to the median value for FFM in the cohort, i.e., 45 kg (e.g., a 1.7-m tall man weighing 51 kg).
c
The model estimated a very large value for the absorption constant, so it was fixed to 50 to stabilize the model without significantly affecting the fit.