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.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D015377:Cilastatin; D003521:Cyclopropanes / Q000494:pharmacology*; D004492:Edetic Acid; D006801:Humans; D015378:Imipenem; D007668:Kidney / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism*; D011817:Rabbits; D013056:Spectrophotometry, Ultraviolet; D013845:Thienamycins / Q000097:blood / Q000378:metabolism*
D003521:Cyclopropanes; D013845:Thienamycins; D015377:Cilastatin; D015378:Imipenem; D004492:Edetic Acid