体内研究
Delafloxacin (the total daily doses vary from 0.156 to 640 mg/kg/24 h, subcutaneous injection) is highly effective against
S. aureus
. Against all four strains are observed a decrease of 1.5 to 2.2 log
10
CFU in organism burden from untreated controls at even the lowest dose studied, and for two strains (MW2 and R2527) there is net bactericidal activity at the lowest dose. At the maximal doses studied, there is a >4-log
10
kill from initial burden for all
S. aureus
strains.
Delafloxacin (2.5, 10, 40, and 160 mg/kg; subcutaneous injection, 24 h) has moderate terminal elimination half-life (t
1/2
=0.68 h, 0.79 h, 0.69 h and 1.0 h for 2.5 mg/kg, 10 mg/kg, 40 mg/kg, and 160 mg/kg, respectively).
Animal Model:
Mice with a neutropenic murine lung infection model (four
S. aureus
, four
S. pneumoniae
, and four
K. pneumoniae
strains)
Dosage:
The total daily doses vary from 0.156 to 640 mg/kg/24 h
Administration:
0.03 to 160 mg/kg are administered every 6 h (q6h) to infected mice by subcutaneous injection
Result:
Inhibited
S. aureus
strains ATCC 29213, ATCC 33591, MW2, R2527 with MICs of 0.008, 0.008, 0.004, and 0.004 mg/L, respectively.
Inhibited
S. pneumoniae
strains ATCC 10813, ATCC 49619, 145, and 1329 with MICs of 0.03, 0.125, 0.016, and 0.016 mg/L, respectively.
Inhibited
K. pneumonia
strains ATCC 43816, 4105, 4110, and 81-1260A with MICs of 0.06, 1, 0.5, and 0.06 mg/L, respectively.
Animal Model:
Neutropenic mice
Dosage:
2.5, 10, 40, and 160 mg/kg; 0.2 mL
Administration:
Subcutaneous injection; 24 h
Result:
The maximum drug concentrations (C
max
) concentrations ranged from 2 to 71 mg/L. AUC
0-∞
values ranged from 2.8 to 152 mg•h/L and were linear across the 2.5- to 160-mg dosing range. The elimination half-life (t
1/2
) ranged from 0.7 to 1 h.
