Table 4. . Population parameter estimates of rifampicin, isoniazid and pyrazinamide pharmacokinetics.
| Parameter description | Typical value (95% CI)† | Random variability (95% CI) |
|---|---|---|
| Rifampicin | ||
| Clearance (l/h)‡ | 22.8 (20.5–25.1) | BSV: 5.5% (0.1–12.3) BOV: 21.3% (11.6–27.9) |
| Volume of central compartment (l)‡ | 77.4 (68.5–85.8) | |
| Bioavailability | 1 FIXED | BOV: 43.4% (33.5–51.1) |
| Ka – absorption rate (1/h)§ | 1.57 (1.25–1.96) PRIOR: 1.04 |
|
| Mean transit time (h)§ | 0.53 (0.46–0.59) PRIOR: 0.62 |
|
| Number of transit compartments§ | 34.6 (33.3–35.8) PRIOR: 34.5 |
|
| Proportional error (%) | 37.4% (32.4–41.1) | |
| Additive error (mg/l) | 0.008 FIXED | |
| Isoniazid | ||
| Clearance (l/h): | ||
| – Fast‡ | 40.5 (35.5; 45.4) | BSV: 26.3% (14.2–33.8) BOV: 13% (3.8–18.8) |
| – Intermediate‡ | 28.4 (24.6–33.1) | |
| – Slow‡ | 17.4 (15.2–20.9) | |
| Volume of central compartment (l)‡ | 73.4 (66.7–83.9) | |
| Inter-compartmental clearance (l/h)‡ | 1.1 (0.7; 1.5) | |
| Volume of peripheral compartment (l)‡ | 19.8 (15.0–27.9) | |
| Bioavailability | 1 FIXED | BOV: 27.4% (19.3–40.3) |
| Absorption lag time (h), prior§ | 0.13 (0.12–0.15) PRIOR: 0.18 |
|
| Ka – absorption rate (1/h), prior§ | 3.9 (3.1– 4.3) PRIOR: 1.85 |
BOV: 23.5% (0.9–97.5) |
| Scaling factor for variability in bioavailability for unobserved doses (-fold)¶ | 3.9 (2.7– 5.0) | |
| Proportional error (%) | 27.8 (20.8– 31.9) | |
| Additive error (mg/l) | 0.004 FIXED | |
| Pyrazinamide | ||
| Clearance (l/h)‡ | 5.41 (4.91– 5.81) | BSV: 19.1% (16.4– 26.0) |
| Volume of central compartment (l)‡ | 62.8 (57.6– 66.3) | BSV: 12.3% (0.1–14.9) |
| Bioavailability | 1 FIXED | BSV: 30.6% (20.8–34.6) BOV: 14.4% (7.8–19.3) |
| Absorption lag Time (h), prior§ | 0.47 (0.42–0.74) PRIOR: 0.49 |
BOV: 74.6 (49.3–84.7) |
| Ka - Absorption rate (1/h), prior§ | 1.26 (1.15–1.83) PRIOR: 3.51 |
BOV: 13.9% (0.1–14.0) |
| Scaling factor for BOV in bioavailability for unobserved doses (-fold)¶ | 2.93 (2.13–5.61) | |
| Proportional Error (%) | 7.78 (6.0–10.9) | |
| Additive error (mg/l) | 1.17 (0.68–1.45) | |
†Obtained with a non-parametric bootstrap (n = 300).
‡All clearance and volume parameters have been allometrically scaled with fat-free mass, and the typical values reported here refer to the typical patient, with fat-free mass of 47 kg.
§These parameters were estimated using a prior.
¶These scaling factors modulate the size of the between-occasion variability in bioavailability for the unobserved doses.
BOV: Between occasion variability; BSV: Between subject variability.