TABLE 1.
Calculated values of key PK parameters for oxacillin and vancomycina
| Study and antibiotic | fAUC0-24 (μg·h/ml) | fAUC0-∞ (μg·h/ml) | t1/2ß (h) | fCmax (μg/ml) | ftrough (μg/ml) | PK-PDb index |
|---|---|---|---|---|---|---|
| Static (part A) | ||||||
| Oxacillin | 384.0 | NA | NA | 16 | 16 | 100% |
| Vancomycin | 480.0 | NA | NA | 20 | 20 | 240-480 |
| Dynamic (part B) | ||||||
| Oxacillin | 19.5 | 19.5 | 0.5 | 4.5 | 0 | 40-65% |
| Vancomycin | 514.9 | 544.2 | 4 | 60/34* | 10/5* | 258-515 |
As the PK profiles for the dynamic simulation were calculated from the values for the key PK parameters derived from the literature, they must be considered theoretical but are representative and therapeutically achievable in plasma after a loading dose of 2 g of vancomycin followed by a maintenance dose of 1 g every 12 h (13, 16). The PK profile of oxacillin was calculated for a 1-g dosage given every 6 h. Abbreviations: fAUC0-24, area under the free concentration-time curve from time zero to 24 h; fAUC0-∞, area under the free concentration-time curve from time zero to infinity; t1/2β, elimination half-life; fCmax, maximum concentration of free drug in plasma; ftrough, trough free concentration; NA, not applicable; *, result obtained with a dose of 1 g.
Taking the appropriate PK-PD parameter into account, the data represent fT > MIC for free oxacillin (expressed as a percentage of the dosing interval) and the ratio of the free area under the concentration-time curve from time zero to 24 h to MIC for vancomycin. The respective MICs used for these calculations were 0.25 to 1.0 μg/ml for oxacillin and 1.0 to 2.0 μg/ml for vancomycin.