Studies on the degradation of imipenem within serum and a renal kidney fraction.

The degradation of imipenem in vitro was analyzed using reversed-phase HPLC. The incubation of imipenem with a microsomal kidney fraction revealed the generation of two metabolites (UV-maxima at 275 or 308 nm, respectively). The metabolism of imipenem by the renal enzyme was completely inhibited by cilastatin (2 micrograms/ml). The lowest detectable inhibitory concentration of cilastatin was at 6.5 X 10(-10) M. The recovery of imipenem from serum was 52.6% after incubation for 2 h at 37 degrees C. The stability of the antibiotic within serum was improved by 13.9% in the presence of EDTA (10 mM) indicating a possible involvement of serum dipeptidases in the systemic breakdown of the imipenem molecule.