TABLE 2.
PK parameter values for levofloxacin in children with MDR-TB disease or exposured
| PK parameter | Typical value (95% CI) | Variability as CV% (95% CI) [eta shrinkage (%)] |
|---|---|---|
| CL (liters/h)a | 4.70 (4.37, 5.00) for HIV− | BSV: 15.2 (10.6, 19.0) [24] |
| Vc (liters)a | 19.2 (10.9, 21.8) | |
| Q (liters/h)a | 0.796 (0.332, 4.76) | |
| Vp (liters)a | 3.40 (2.53, 38.7) | |
| Tlag (h) | 0.242 (0.0385, 0.654) for oral dosing | BOV: 130 (30.9, 303) [76] |
| ka (1/h) | 1.61 (0.855, 2.78) | BOV: 64.8 (43.4, 80.9) [43] |
| F | 1 (fixed) | BOV: 21.8 (13.7, 28.4) [10] |
| HIV+ on CL (%) | −15.9 (−26.6, −5.93) | |
| NGT on Tlag (%) | −85.6 (−99.3, −34.6) | |
| Scaling of BOV in F for unobserved doses (fold)b | 4.48 (3.31, 7.08) | |
| PMAGE50 (mo) | 10.6 (7.55, 12.9) | |
| γ | 3.39 (1.42, 4.98) | |
| Additive error (mg/liter)c | 0.0160, i.e., 20% of LLOQ (fixed) | |
| Proporational error (%) [epsilon shrinkage (%)] | 11.6 (10.0, 12.7) [29] |
All clearance and volume parameters have been scaled with allometric scaling. The typical values reported here refer to a 12-kg child aged 2 years. Age affects clearance, since maturation was used. At 2 years after birth, maturation is predicted to be 97.9% complete.
This is a multiplicative factor increasing the BOV in bioavailability for all predose concentrations, which follow an unobserved dose.
The estimate of the additive error hit the stipulated lower boundary (20% of LLOQ), so it was fixed to this value.
Values in parentheses are empirical 95% confidence intervals obtained with a 500-sample nonparametric bootstrap. The PK parameter variability was included either as between-subject variability or between-occasion variability, assuming a lognormal distribution. It is reported here as the approximate coefficient of variation (in percent). CL, clearance; Vc, central volume of distribution; Q, intercompartmental clearance; Vp, peripheral volume of distribution; Tlag, absorption lag time; ka, absorption rate constant; F, bioavailability; PK, pharmacokinetic; PMAGE50, postmenstrual age at which 50% maturation is reached; γ, shape factor for the maturation function; BSV, between-subject variability; BOV, between-occasion variability; HIV+ and HIV− HIV-infected and uninfected children, respectively; NGT, drug administration with a nasogastric tube.