Table 2.
Parameter estimates of the final model describing quinine population pharmacokinetics in children (n = 75) with severe malaria
| Effect and variable | Population estimatea (%RSEb) | 95% CIb |
|---|---|---|
| Fixed PK effects | ||
| CL/F (liters/h) | 0.792 (6.42) | 0.698–0.898 |
| V/F (liters) | 13.7 (6.56) | 12.1–15.6 |
| DUR (h) | 1.42 (21.1) | 0.486–1.70 |
| Fixed PD effects | ||
| Baseline hazard (h−1) | 0.016 (42.7) | 0.00586–0.0342 |
| AUC50 (h · mg/liter) | 64.8 (96.9) | 21.8–387 |
| Random PK effects | ||
| ηCL/F | 0.128 (28.7) | 0.0620–0.201 |
| ηV/F | 0.176 (25.7) | 0.0927–0.262 |
| ηCL/F ∼ ηV/F | 0.15 (21.5) | 0.0835–0.206 |
| σ | 0.0942 (7.76) | 0.0671–0.124 |
| Post hoc PK estimatesc | ||
| CL/F (liters/h/kg) | 0.0741 | 0.0455–0.144 |
| V/F (liters/kg) | 1.24 | 0.645–2.89 |
| t1/2 (h) | 12.1 | 9.63–14.3 |
| Cmax (mg/liter) | 13.4 | 7.20–24.8 |
| AUC0–7.5 h (h · mg/liter) | 78.9 | 42.3–148 |
Computed population mean values from NONMEM are calculated for a typical patient with a body weight of 11 kg.
Assessed by the nonparametric bootstrap method (n = 1,586 successful iterations out of 2,000 for pharmacokinetics [PK] and n = 1,532 successful iterations out of 2,000 for pharmacodynamics [PD]) for the final model. The relative standard error (%RSE) is calculated as 100 × (standard deviation/mean value). The 95% confidence intervals (CIs) are displayed as the 2.5 to 97.5 percentiles of bootstrap estimates.
Post hoc estimates are displayed as median values with 2.5 to 97.5 percentiles of empirical Bayes estimates.
CL/F, elimination clearance; V/F, volume of distribution; F, intramuscular bioavailability; DUR, duration of zero-order absorption; baseline hazard, baseline hazard of death per hour in the time-to-event model; AUC50, cumulative exposure associated with a 50% reduction in the baseline hazard of death; η, interindividual variability; ηCL/F ∼ ηV/F, correlation of random effects on CL/F and V/F; σ, additive residual variance error; t1/2, terminal elimination half-life; AUC0–7.5 h, area under the concentration-time curve from 0 to 7.5 h; Cmax, predicted peak concentration after the first dose.