TABLE 2.
Plasma pharmacokinetic parameters for RWJ-416457 and linezolid in CF-1 mice
| Compound | Administration route | Dose (mg/kg) | AUC24 (h·μg/ml) | fAUC24a (h·μg/ml) | Cmax (μg/ml) | fCmax (μg/ml) | Tmaxb (h) | t1/2 (h) | CL (ml/h/kg) | CL/Fc (ml/h/kg) |
|---|---|---|---|---|---|---|---|---|---|---|
| RWJ-416457 | i.v.d | 2 | 3.2 | 1.7 | 4.4 | 2.4 | NAe | 1.5 | 630 | |
| Linezolid | i.v.d | 2 | 2.1 | 1.4 | 3.3 | 2.3 | NA | 0.5 | 940 | |
| RWJ-416457 | s.c. | 10 | 15 | 8.3 | 7.5 | 4.1 | 0.5 | 2.0 | 650 | |
| Linezolid | s.c. | 10 | 16 | 11 | 11 | 7.1 | ≤0.13 | 0.8 | 640 | |
| RWJ-416457 | p.o. | 10 | 23 | 13 | 3.5 | 1.9 | 2.0 | 3.4 | 430 | |
| Linezolid | p.o. | 10 | 19 | 13 | 8.9 | 6.0 | ≤0.13 | 1.4 | 520 |
a
The free-drug plasma exposure following a single 10-mg/kg dose (p.o. and s.c.) or a single 2-mg/kg dose (i.v.) was determined from the total drug plasma levels corrected for protein binding.
b
Tmax, time to maximum concentration of drug in serum.
c
CL/F, CL adjusted for bioavailability.
d
Normalization of i.v. values to a 10-mg/kg dose (assuming linear response) yielded RWJ-416457 and linezolid AUC24 values of 16 and 11 h·μg/ml, respectively, and fAUC24 values of 8.5 and 7 h·μg/ml, respectively.
e
NA, not applicable.