Dose | Peak | T1/2β | AUC0–24h | Peak/MIC ratio | AUC/MIC ratio | AUC>MIC1-b | ΔtMIC |
---|---|---|---|---|---|---|---|
mg/kg | μg/ml | h | μg/ml · h | μg/ml · h | h | ||
CPFX | |||||||
25 | 5.4 (1.4) | 1.2 (0.2) | 9.1 (2.8) | 7.2 (1.8) | 12 (4) | 5.8 (2.1) | 4.0 (0.5) |
50 | 5.7 (0.4) | 1.8 (0.1) | 19 (4) | 7.6 (0.6) | 26 (5) | 12 (3) | 6.5 (0.9) |
75 | 9.4 (1.9) | 1.9 (0.2) | 26 (9) | 13 (2) | 34 (11) | 18 (8) | 7.5 (0.8) |
100 | 12 (3) | 2.0 (0.2) | 32 (12) | 16 (4) | 43 (16) | 24 (12) | 8.5 (1.3) |
150 | 17 (2) | 2.1 (0.3) | 48 (13) | 22 (3) | 64 (17) | 36 (12) | 10 (1) |
200 | 20 (7) | 3.1 (0.6) | 97 (36) | 26 (10) | 129 (47) | 83 (31) | 16 (2) |
SPFX | |||||||
6.25 | 1.3 (0.2) | 2.0 (0.2) | 5.1 (1.5) | 5.2 (0.8) | 20 (6) | 2.8 (1.0) | 5.2 (1.1) |
12.5 | 1.9 (0.3) | 2.4 (0.5) | 8.1 (2.7) | 7.6 (1.1) | 32 (11) | 6.0 (0.9) | 8.0 (1.4) |
25 | 3.7 (0.2) | 2.5 (0.5) | 19 (7) | 15 (1) | 75 (27) | 16 (5) | 12 (1) |
50 | 4.6 (0.8) | 5.0 (0.3) | 36 (5) | 18 (3) | 143 (20) | 29 (5) | 22 (2) |
↵1-a Data are mean values (S.D.) for three experiments (three mice per group in each experiment).
↵1-b AUC>MIC refers to the AUC above the MIC and ΔtMIC to the time during which concentrations in serum exceeded the MIC for the challenge organism (S. pneumoniae P4241), i.e., 0.75 and 0.25 μg/ml for CPFX and SPFX, respectively.