TABLE 1.
Calculated pharmacokinetic and pharmacodynamic variables for various dosage regimens tested in the dose fractionation studiesa
| Total dose (mg/kg/24 h) | Dose (mg/kg) | Time point(s) (h) | Cmax | T > MIC | AUC0-24 |
|---|---|---|---|---|---|
| 0.5 | 0.167 | 0, 8, and 16 | 0.37 | 0.00 | 2.13 |
| 0.25 | 0 and 12 | 0.53 | 0.25 | 2.16 | |
| 0.5 | 0 | 1.03 | 0.50 | 2.14 | |
| 1.0 | 0.25 | 0, 6, 12, and 18 | 0.59 | 0.75 | 4.19 |
| 0.33 | 0, 8, and 16 | 0.74 | 0.75 | 4.24 | |
| 0.5 | 0 and 12 | 1.06 | 1.25 | 4.31 | |
| 1.0 | 0 | 2.06 | 2.50 | 4.29 | |
| 2.0 | 0.666 | 0, 8, and 16 | 1.48 | 4.50 | 8.48 |
| 1.0 | 0 and 12 | 2.11 | 5.50 | 8.62 | |
| 2.0 | 0 | 4.11 | 5.50 | 8.58 | |
| 4.0 | 1.0 | 0, 6, 12, and 18 | 2.35 | 14.25 | 16.74 |
| 4 | 0 | 8.23 | 8.25 | 17.16 | |
| 16.0 | 4.0 | 0, 6, 12, and 18 | 9.40 | 24.00 | 66.96 |
| 16 | 0 | 32.90 | 14.25 | 68.62 |
a
Concentrations represent free (unbound) concentrations, assuming 85% protein binding (mouse plasma protein binding estimated using human data).