TABLE 1.
Values of pharmacokinetic and pharmacodynamic parameters for levofloxacin, moxifloxacin, and trovafloxacin following administration of 50 and 100 mg/kg/day for 5 days in EtOH-fed, pair-fed, and chow-fed rats with pneumococcal pneumonia
| Group and parameter | Levofloxacin
|
Moxifloxacine
|
Trovafloxacin
|
|||
|---|---|---|---|---|---|---|
| 50 mg/kg | 100 mg/kg | 50 mg/kg | 100 mg/kg | 50 mg/kg | 100 mg/kg | |
| Ethanol fed | ||||||
| Serum Cmax (μg/ml) | 8.1 ± 3.0 | 12.2 ± 3.0 | 15.1 ± 6.6 | 22 ± 8.6 | 7.7 ± 1.5 | 13.4 ± 3.7 |
| AUC0-24 (μg · h/ml) | 44.9 ± 14.4 | 63 ± 16.6 | 39.6 ± 9.7 | 75.2 ± 14.3 | 36.8 ± 10.8 | 69.9 ± 16.1 |
| fAUC (μg · h/ml) | 37.3 ± 11.9 | 52.3 ± 13.7 | 21.9 ± 5.4 | 41.6 ± 7.9 | 12.9 ± 3.4 | 24.5 ± 5.6 |
| ELF vol (μg/ml) | 1.2 ± 0.6 | 2.5 ± 1.0 | 3.9 ± 1.3 | 7.3 ± 1.7 | 1.9 ± 0.9 | 2.7 ± 1.4 |
| WBC (μg/ml)a | 3.1 ± 2.2 | 5.9 ± 3.0 | 4.2 ± 1.9 | 6.9 ± 3.7 | 1.9 ± 1.2 | 3.8 ± 2.4 |
| PBb (%) | 17.2 | 44.7 | 64.9 | |||
| Cmax/MICc | 6.7 ± 2.4 | 10.1 ± 2.5 | 43.9 ± 19.2 | 64.0 ± 24.9 | 5.7 ± 1.2 | 18.8 ± 5.2 |
| AUC/MICd | 37.3 ± 11.9 | 52.3 ± 13.7 | 115.3 ± 28.2 | 218.9 ± 41.6 | 51.7 ± 15.2 | 98.1 ± 22.6 |
| CL (ml/min/kg) | 21.1 ± 1.8 | 29.2 ± 1.2 | 11.6 ± 0.8 | 16.9 ± 1.0 | 12.2 ± 1.3 | 18.9 ± 1.1 |
| Pair fed | ||||||
| Serum Cmax (μg/ml) | 7.5 ± 3.0 | 12.4 ± 4.2 | 10.0 ± 5.8 | 17.5 ± 7.1 | 7.0 ± 1.5 | 9.8 ± 3.9 |
| AUC0-24 (μg · h/ml) | 34.2 ± 11.9 | 57.7 ± 17.2 | 32.7 ± 12.9 | 65.3 ± 15.4 | 31.0 ± 11.2 | 51.9 ± 17.9 |
| fAUC (μg · h/ml) | 24.4 ± 8.5 | 41.2 ± 12.3 | 12.5 ± 4.9 | 24.9 ± 5.9 | 5.8 ± 2.1 | 9.7 ± 3.3 |
| ELF vol (μg/ml) | 1.9 ± 0.8 | 2.7 ± 0.8 | 2.1 ± 1.9 | 3.7 ± 1.2 | 1.7 ± 0.8 | 2.9 ± 1.1 |
| WBC (μg/ml) | 2.1 ± 1.4 | 3.7 ± 2.1 | 3.9 ± 2.0 | 5.0 ± 3.3 | 1.3 ± 1.0 | 3.1 ± 1.8 |
| PB (%) | 28.6 | 61.9 | 81.4 | |||
| Cmax/MIC | 5.4 ± 2.1 | 8.9 ± 3.0 | 20.6 ± 11.9 | 35.1 ± 14.2 | 5.9 ± 1.1 | 7.3 ± 2.9 |
| AUC/MIC | 24.4 ± 8.5 | 41.2 ± 12.3 | 67.3 ± 26.5 | 130.9 ± 31.3 | 23.1 ± 9.4 | 38.6 ± 13.3 |
| CL (ml/min/kg) | 22.3 ± 0.9 | 28.1 ± 1.2 | 12.7 ± 0.7 | 17.3 ± 1.1 | 11.8 ± 1.0 | 14.5 ± 0.9 |
| Chow fed | ||||||
| Serum Cmax (μg/ml) | 6.6 ± 1.5 | 9.3 ± 3.7 | 10.6 ± 1.7 | 14.5 ± 4.8 | 6.1 ± 2.1 | 11.9 ± 3.9 |
| AUC0-24 (μg · h/ml) | 35.7 ± 13.3 | 54.9 ± 17.1 | 34.8 ± 12.1 | 67.9 ± 15.7 | 28.9 ± 8.9 | 52.7 ± 14.8 |
| fAUC (μg · h/ml) | 25.4 ± 9.4 | 39.0 ± 12.1 | 14.1 ± 4.9 | 27.4 ± 6.4 | 4.9 ± 1.5 | 8.9 ± 2.5 |
| ELF vol (μg/ml) | 2.0 ± 0.6 | 2.9 ± 1.0 | 3.4 ± 1.3 | 5.9 ± 1.5 | 1.9 ± 0.8 | 2.7 ± 0.6 |
| WBC (μg/ml) | 2.5 ± 1.1 | 4.2 ± 2.9 | 3.5 ± 1.7 | 4.6 ± 2.2 | 1.4 ± 0.9 | 3.2 ± 1.4 |
| PB (%) | 29.0 | 59.5 | 83.1 | |||
| Cmax/MIC | 4.7 ± 1.1 | 6.6 ± 2.6 | 22.6 ± 3.6 | 30.9 ± 10.2 | 4.1 ± 1.6 | 8.1 ± 2.6 |
| AUC/MIC | 25.4 ± 9.4 | 39.0 ± 12.1 | 74.2 ± 25.8 | 144.7 ± 33.5 | 19.5 ± 6.0 | 35.6 ± 10.0 |
| CL (ml/min/kg) | 22.9 ± 1.4 | 29.7 ± 1.3 | 12.3 ± 0.9 | 16.2 ± 1.0 | 12.8 ± 1.2 | 15.9 ± 1.4 |
a
White blood cells from BAL fluid.
b
PB, protein binding of the antibiotic in percent.
c
Calculated by using the antibiotic free fraction.
d
Calculated by using the antibiotic free fraction.
e
Moxifloxacin Free AUC/MIC and Cmax/MIC ratios for moxifloxacin were significantly greater than those for either levofloxacin and trovafloxacin at equivalent doses (P < 0.05).