TABLE 1.
Pharmacokinetic Indices
| ID | First Dose | Multiple Doses | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
| ||||||||||||
| Dose (mg/kg) | CL (mL/h/kg) | V (L/kg) | t1/2 (h) | T>MIC (%) | AUC0–24 (h* mg/L) | Dose (mg/kg) | CL (mL/h/kg) | V (L/kg) | t1/2 (h) | T>MIC (%) | AUC0–24 (h* mg/L) | |
| 1 | 25 | 19 | 1.3 | 47 | 63 | 367 | 25 | 22 | 1.5 | 46 | 61 | 385 |
| 2 | 25 | 22 | 1.7 | 55 | 61 | 288 | 25 | 19 | 1.9 | 68 | 83 | 352 |
| 3 | 25 | 10 | 1.7 | 116 | 132 | 324 | 25 | 9 | 2.3 | 189 | 233 | 399 |
| 4 | 25 | 17 | 1.5 | 60 | 75 | 343 | - | - | - | - | - | - |
| 5 | 25 | 33 | 1.4 | 29 | 39 | 322 | 25 | 33 | 1.4 | 29 | 38 | 347 |
| 6 | 25 | 16 | 1.7 | 75 | 85 | 307 | 25 | 11 | 1.9 | 115 | 152 | 424 |
| 7* | - | - | - | - | - | - | 12 | 22 | 2.2 | 56 | 438 | 299† |
| 8 | 25 | 14 | 1.7 | 79 | 91 | 316 | - | - | - | - | - | - |
| 9 | 25 | 44 | 1.3 | 21 | 28 | 303 | 25 | 35 | 1.4 | 27 | 39 | 344 |
| 10 | 25 | 11 | 1.2 | 76 | 106 | 423 | - | - | - | - | - | - |
|
| ||||||||||||
| Median | 17 | 1.5 | 60 | 75 | 322 | 22 | 1.9 | 56 | 83 | 352 | ||
| IQR | 14, 22 | 1.3, 1.7 | 47, 76 | 61, 91 | 307, 343 | 11, 33 | 1.4, 2.2 | 37, 92 | 39, 233 | 344, 399 | ||
*
Infant 7 was on fluconazole per standard of care (12 mg/kg IV daily), and PK sampling occurred after the final (seventh) dose. All other multiple-dose data were obtained during the infants’ second dose.
†
T>MIC and AUC0–24 for infant 7 were obtained by simulating exposure after a dose of 25 mg/kg using clearance and volume of distribution derived from the 1-compartment model.
CL indicates clearance; V, volume of distribution; t1/2, half-life; T>MIC, percentage of the dosing interval that fluconazole concentration was above the minimum inhibitory concentration of 4 mg/L (PD target was 50% of dosing interval); AUC0–24,area under the curve from 0–24 hours (PD target 400 h*mg/L); IQR, interquartile range.