TABLE 2.

Plasma pharmacokinetic parameters for RWJ-416457 and linezolid in CF-1 mice

CompoundAdministration routeDose (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-416457i.v.d23.21.74.42.4NAe1.5630
Linezolidi.v.d22.11.43.32.3NA0.5940
RWJ-416457s.c.10158.37.54.10.52.0650
Linezolids.c.101611117.1≤0.130.8640
RWJ-416457p.o.1023133.51.92.03.4430
Linezolidp.o.1019138.96.0≤0.131.4520
  • 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.