Table 2.
Final model parameter estimates for high-dose rifampicin pharmacokinetics in children <12 years of age with TB in the Opti-Rif trial
| Parameter | Value | 95% CI |
|---|---|---|
| Intrinsic clearancea (L/h) | 54.4 | 44.0–68.4 |
| Volume of distributionb (L) | 15.0 | 13.5–16.5 |
| Rate of absorption (1/h) | 2.06 | 1.55–2.96 |
| Mean absorption transit time (h) | 0.368 | 0.252–0.478 |
| Number of absorption transit compartments | 13.0 | 10.5–16.7 |
| Liver blood flowc (L/h) | 90 FIXED | |
| Liver volumec (L) | 1 FIXED | |
| Rifampicin fraction unbound in plasma | 0.2 FIXED | |
| K m – Michaelis constant for saturation of clearance (mg/L) | 9.48 | 6.69–14.3 |
| Post-menstrual age with 50% clearance maturation (years) | 1.24 | 1.15–1.31 |
| Shape factor for clearance maturation function | 10.2 | 5.27–16.7 |
| Bioavailability at birth relative to 1 | 0.689 | 0.561–0.831 |
| Age when bioavailability reaches maximum (years) | 3 FIXED | |
| Inter-individual variability intrinsic clearance (CV%) | 25.3% | 19.5%–31.9% |
| Inter-occasional variability bioavailability (CV%) | 31.2% | 25.9%–37.6% |
| Inter-occasional variability rate of absorption (CV%) | 152% | 112%–224% |
| Inter-occasional variability mean transit time (CV%) | 132% | 94.3%–214% |
| Proportional error (%) | 21.1 | 19.9–24.4 |
| Additive error (mg/L) | 0.0766 | 0.0618–0.0901 |
CV%, coefficient of variation.
a
For a child with a fat-free mass of 9 kg.
b
For a child with total body weight of 12 kg.
c
Values for an adult with a fat-free mass of 56 kg, scaled allometrically with fat-free mass.