Table 2. In vivo pharmacokinetic parameters in plasma for bicyclic 4-nitroimidazole analogs.
| CompoundID | Dose(mg/kg) | p.o. PK parameters | i.v. PK parametersa | ||||||
| Cmax(µg/mL) | AUC24(µg.h/mL) | Tmax(hr) | T1/2(p.o.) | F (%) | Vss(L/kg) | CL(mL/min/kg) | T1/2(i.v) | ||
| PA-824* | 25 | 6.0 | 50.9 | 2 | 2.7 | 100 | 1.6 | 12.1 | 1.6 |
| NI-622* | 50 | 14.8 | 108.4 | 4 | 2.1 | 100 | 1.8 | 14.7 | 1.8 |
| NI-644* | 50 | 16.2 | 89.5 | 1 | 3.6 | 100 | 0.7 | 9.5 | 0.9 |
| Amino-824* | 10 | 1.7 | 6.0 | 0.3 | 2.0 | 74 | 2.3 | 20.5 | 2.0 |
| AminoEthyl-824* | 10 | 1.0 | 2.9 | 1 | 1.7 | 76 | 2.0 | 44.0 | 0.7 |
| NI-135∧ | 25 | 1.2 | 4.8 | 0.5 | 2.9 | 51 | 4.2 | 41.0 | 4.0 |
| NI-147∧ | 25 | 0.04 | 0.02 | 0.1 | 0.2 | 0.3 | 0.4 | 70.8 | 0.3 |
| NI-136∧ | 25 | 2.0 | 10.7 | 0.5 | 2.0 | 64 | 1.8 | 25.1 | 1.3 |
| NI-176∧ | 25 | 2.2 | 13.7 | 1 | 4.3 | 86 | 1.8 | 22.2 | 1.0 |
| NI-269∧ | 25 | 2.8 | 16.0 | 0.3 | 3.8 | 88 | 2.6 | 19.7 | 2.1 |
| NI-182∧ | 25 | 3.5 | 22.5 | 0.5 | 2.0 | 82 | 3.0 | 15.2 | 2.8 |
| NI-145∧ | 25 | 1.8 | 16.2 | 2 | 4.2 | 68 | 1.7 | 17.0 | 2.0 |
| NI-297∧ | 25 | 6.0 | 99.1 | 8 | 4.9 | 100 | 2.6 | 5.0 | 6.7 |
| NI-302∧ | 25 | 12.9 | 144.1 | 4 | 4.1 | 100 | 1.2 | 4.3 | 3.7 |
a
i.v dosing at either 10 mg/kg* or 5 mg/kg∧.
Cmax = maximum concentration reached in plasma, AUC24 = exposure between 0 to 24 h, Tmax = time to reach maximum concentration, T1/2 = half-life, F = oral bioavailability, Vss = volume of distribution at steady state, CL = total systemic clearance.