Table 4. In vivo pharmacodynamics of bicyclic 4-nitroimidazole analogs studied in mice.
| Mean log lung CFU ± SEM | ΔMean log lung CFU reduction ± SEM | ||||
| Dose (mg/kg) | Vehicle control | 25 | 100 | 25 | 100 |
| PA-824 | 6.07±0.12 | 4.67±0.37 | 4.12±0.13 | 1.40±0.37 | 1.95±0.13 |
| 6.24±0.02 | 4.67±0.10 | 3.93±0.09 | 1.57±0.10 | 2.31±0.09 | |
| 6.66±0.14 | 5.20±0.05 | 4.19±0.11 | 1.46±0.05 | 2.47±0.11 | |
| 1.48±0.09$ | 2.30±0.08$ | ||||
| NI-622 | 6.66±0.14 | 5.77±0.08 | 5.85±0.11 | 0.89±0.08* | 0.81±0.11* |
| NI-644 | 6.66±0.14 | 6.18±0.03 | 6.09±0.07 | 0.48±0.03* | 0.57±0.07* |
| Amino-824 | 6.22±0.08 | nd | 5.14±0.08 | nd | 1.08±0.08* |
| AminoEthyl-824 | 6.22±0.08 | nd | 4.53±0.07 | nd | 1.69±0.07ns |
| NI-135 | 6.24±0.02 | 4.76±0.07 | 4.36±0.07 | 1.48±0.07ns | 1.88±0.07ns |
| NI-136 | 6.24±0.02 | 4.93±0.06 | 4.18±0.17 | 1.31±0.06ns | 2.06±0.17ns |
| NI-182 | 6.07±0.12 | 4.84±0.14 | 4.81±0.18 | 1.23±0.14ns | 1.26±0.18* |
| NI-297 | 6.07±0.12 | 4.51±0.11 | nd | 1.56±0.11ns | nd |
| NI-302 | 6.62±0.11 | nd | 4.45±0.22 | nd | 2.17±0.22ns |
The mean log lung CFU’s in five independent in vivo efficacy studies ranged between 6.07 and 6.66 in untreated infected mice.
nd = not determined.
Δ
Mean log lung CFU reduction compared to untreated controls. Each data represents mean value ± SEM from 5 animals.
$
Mean value from three independent experiments (n = 15).
*Significant difference at P<0.05 compared to respective PA-824 doses.
ns
No significant difference at P<0.05 compared to respective PA-824 doses.