1-$eta$-Methyl carbapenem-2-substituted pyrroudine derivatives. CRB 529 and CRB 550, were synthesized as investigational carbapenem derivatives. It has been reported that the in vitro antibacterial activities of the compounds against G(+) and G(-) bacteria were almost the same or more effective than those of imipenem (IPM) and meropenem (MEPM), and also showed better in vivo efficacy than MEPM and inlipeneni/cilastatin (IPM/CS) against representative G(-) organisms, P. aeruginosa and MRSA organisms, S. aureus. The antibacterial activities, pharmacokinetics and protective efficacy of IPM/CS and CRB 529 and CRB 550 wereconducted after subcutaneous or intravenous administration to mice and rats. The pharmacokinetic parameters of CRB 529 and CRB 550 in mice were as follows: the observed maximal serum concentrations (C$_{max}$) following I.V. administration were 87.5 and 101 $mu extrm{g}$/ml for CRB 529 and CRB 550, respectively, and 63.6 $mu extrm{g}$/ml for IPM/CS. The half-lives (t$_{1/2}$) were 14.0 and 12.0 n-dn for CRB 529 and CRB 550, respectively, and 14.8 min for IPM/CS. In rats, $C_{max}$ after I.V. administration were 74.0 and 91.8 $mu extrm{g}$/ml for CRB 529 and CRB 550, respectively, and 41.2 $mu extrm{g}$/ml for IPM/CS. The tissue levels of CRB 529 and CRB 550 and IPM/CS after I.V. administration at a dose of 20 mg/kg decreased by the following order: lung, heart, kindney, liver and spleen for CRB 529, lddney, liver. lung, heart and spleen for CRB 550 and kidney, lung, liver, heart, spleen and brain for IPM/CS. In systemic infection, CRB 529 and CRB 550 showed excellent efficacies against P. aeruginosa and S. aureus (MRSA) at a dose of 5 mg/kg. The PD$_{50s}$ were 0.80, 0.36 mg/kg for CRB 529 and CRB 550, respectively, and 3.22 mg/kg for IPM/CS against P. aeruginosa. The corresponding values against S. aureus (MRSA) were 76.0, 55.3 mg/kg for CRB 529 and CRB 550, respectively, and 146 mg/kg for IPM/CS. In local infection, the antibacterial activities of CRB 529 and CRB 550 were more effective than those of IPM/CS against intrarenal infection with E. coli and P. aeruginosa and also showed as effective as IPM/CS against respiratory tract infection with E. coli and P. aeruginosa at a dose of 5 mg/kg.