TABLE 3.
Pharmacokinetic and pharmacodynamic parameters for levofloxacin and ceftriaxone following a single intravenous dose 18 h postinfection
| Parametera | Data (mean ± SD) for the indicated antibiotic in the indicated tissue |
|||
|---|---|---|---|---|
| 150 mg/kg levofloxacin |
50 mg/kg ceftriaxone |
|||
| Serum | Lungs | Serum | Lungs | |
| Pharmacokinetics | ||||
| Cmax (mg/liter) | 9.8 ± 2.03 | 40.9 ± 5.36 | 44.5 ± 3.5 | 38.7 ± 7.9 |
| AUC0–24 (mg · h/liter) | 92.64 ± 9.08 | 146.26 ± 23.37 | 97.6 ± 11.23 | 79.5 ± 8.36 |
| t1/2 (h) | 12.37 ± 3.21 | 12.06 ± 2.67 | 1.51 ± 0.67 | 1.12 ± 0.47 |
| CL | 1.62 ± 0.16 | 1.02 ± 0.07 | 0.51 ± 0.05 | 1.29 ± 0.19 |
| Pharmacodynamics | ||||
| AUC/MIC (h) | 5.79 ± 1.42 | 9.14 ± 1.33 | 48.8 ± 5.61 | 39.75 ± 4.18 |
| T>MIC (h) | —b | 16.47 ± 2.48 | 9.19 ± 2.21 | 7.64 ± 1.12 |
| Cmax/MIC | 0.619 ± 0.12 | 2.56 ± 0.29 | 22.25 ± 0.25 | 19.35 ± 3.95 |
Cmax, maximum concentration of drug in serum; t1/2, time taken to reach half of the maximum concentration; AUC, area under the concentration-time curve from time zero to 24 h after antibiotic treatment; T>MIC, time during which the drug concentration remains above the MIC in serum; AUC/MIC, ratio of the area under the curve during 24 h of antibiotic treatment to the MIC for the S. pneumoniae strain AMRI-SP1; Cmax/MIC, ratio of maximum concentration of the drug achieved in serum to the MIC of the drug.
—, the peak drug concentration achieved in serum was below the MIC of levofloxacin (16 mg/liter) for the MDR strain AMRI-SP1 but was quite above the sub-MIC level of 0.5 mg/liter (1/32× MIC) used for the time-kill assay in vitro using the same isolate.