Table 2. Population pharmacokinetic parameters of fluconazole determined in juvenile mice, neonates and adults.
| PK parameters | Juvenile mice | Neonates | Adults | ||
|---|---|---|---|---|---|
|
| |||||
| Final estimate (RSE) | Bootstrap median(2.5th – 97.5th) | Final estimate (RSE) | Bootstrap median(2.5th – 97.5th) | Final estimate | |
| Absorption rate constant Ka (h-1) | 16.2 (FIX) | 3.38 | |||
| Lag-time (h) | 0.23 | ||||
| Volume of distribution V (L) | 55.7 | ||||
| V= θ1 × (weight /median) θ2 | |||||
| θ1 | 0.006 (2.4) | 0.006 (0.003-0.006) | 3.0 (6.5) | 3.0 (2.6-3.4) | |
| θ2 | 0.628 (5.6) | 0.627 (0.542-0.7) | 0.907 (8.8) | 0.920 (0.699-1.179) | |
| Clearance CL (L/h) | 1.18 | ||||
| CL/F= θ3 × (weight /median) θ4× Fage | |||||
| θ3 | 0.00017 (15.7) | 0.00016 (0.00009-0.00022) | 0.0521(14.4) | 0.0519 (0.0370-0.0673) | |
| θ4 | 0.362 (38.4) | 0.372 (0.116-0.758) | 0.922 (25.6) | 0.897 (0.361-1.520) | |
| Fage (mice) = θ6 + EXP (θ5*PNA-9) | |||||
| θ5 | 0.468 (8.4) | 0.469 (0.394-0.588) | |||
| θ6 | 1.21 (23.5) | 1.26 (0.78-2.41) | |||
| Fage (neonates) = (GA/median) θ7 | 2.88 (25.3) | 2.89 (0.59-7.28) | |||
| Interindividual variability (%) | |||||
| Ka | 177.8 | ||||
| V | 19.1 (42.1) | 17.3 (8.1-24.2) | 17.4 | ||
| CL | 14.0 (35.4) | 13.0 (5.9-17.6) | 35.1 (30.6) | 30.1 (12.7-43.8) | 22.2 |
| Residual variability | |||||
| Proportional (%) | 11.0 (40.5) | 10.2 (5.8-15.6) | 15.0 (31.5) | 14.6 (10.7-20.0) | 14.7 |
| Additive (mg/L) | 0.08 | ||||
The median weight of juvenile mice and neonates are 6.52g and 3kg, respectively