TABLE 1.
Population PK parameter estimates for one- or two-compartment models describing plasma and lung ELF concentrations of five aminoglycosides after intravenous (or intramuscular) dosinga
| Drug | Population | AUCELF/AUCPlasma | t1/2,eq (h) | CL (L/h) | CLd (L/h) | V1 (L) | V2 (L) | ||
|---|---|---|---|---|---|---|---|---|---|
| Mean (RSEc) | BSVb (RSEc) | Median [range] | Mean | Mean | Mean | Mean | Mean | ||
| Amikacin | ICU patients (with VAP) | 0.502 (31%) | 0.844 (39%) | 0.461 [0.138–1.60] | 5.80 (58%) | 4.88 | 24.6 | ||
| Amikacin | Ventilated neonates | 0.138 | 1.61 | ||||||
| Arbekacin | Healthy volunteers | 0.535 (12%) | 0.10 (fixed) | –f | 0.613 (24%) | 3.56 | 6.77 | 3.00 | 4.77 |
| Gentamicin | VABP critically ill patients | 0.600 (7%) | 0.165 (160%) | 0.600 [0.507–0.782] | 0.857 (18%) | 3.63 | 14.9 | 13.5 | 13.9 |
| Netilmicin | ICU patients (ventilated, with pneumonia)e | 1.00 (11%) | 0.276 (67%) | 0.989 [0.627–1.94] | 1.68 (13%) | 5.61 | 6.90 | 9.36 | 7.87 |
| Tobramycind | VABP critically Ill patients and healthy volunteers | 0.642 (9%) | 0.248 (84%) | 0.635 [0.468–0.901] | 3.38 (17%) | 5.60 | 20.1 | ||
The volume of distribution of the ELF compartment was set to a small, non-influential value (0.1 L). The estimated ELF-to-plasma equilibration half-life characterized the extent of system hysteresis. AUCELF, area under the ELF concentration time curve from time zero to infinity (for a single aminoglycoside dose); AUCPlasma, area under the plasma concentration time curve from time zero to infinity (for a single aminoglycoside dose); ICU, intensive care unit; t1/2,eq, equilibration half-life between the ELF and the plasma compartment. This half-life characterizes the extent of system hysteresis and represents the slower rise of ELF concentrations compared to the rapid rise of the plasma or serum concentrations. If an aminoglycoside was dosed as a continuous infusion, the t1/2,eq would be the half-life of approaching a constant steady-state concentration in ELF; VAP / VABP, ventilator-associated (bacterial) pneumonia.
BSV, between subject variability reported as coefficient of variation.
Relative standard errors.
The estimated absorption half-life (t1/2,abs) after intramuscular dosing of tobramycin was 13.4 min.
Patients were intubated and ventilated for a variety of reasons and received antibiotics due to the development of pneumonia.
Not applicable.